This Plumping Moisturizer Delivers ‘Visible Wrinkle Reduction’ In Days — And It’s On Sale

The best kept secret to actually impactful skin care for mature skin isn’t rocket science; it’s actually simple: A gooooood moisturizer. The world likes to sell you on magical serums that disappear wrinkles and red light therapy gadgets for hands-free spa results, but any beauty expert will tell you, a well-hydrated face is your best face. If you’re looking for something lightweight and moisturizing to bring the bounce-back to your face in this ultra-drying spring heat, consider this MVP: The daily plumping, collagen and peptide moisturizer gel from Paula’s Choice. Reviewers swear it hydrates like a dream, actually addresses wrinkles well — and it’s the lowest price since BLACK FRIDAY at 30% off.

Made with a three-part peptide blend, the satin-like gel is designed to bring a “visible wrinkle reduction” — fast.

The brand says the peptide blend, specifically oligopeptide, helps your skin produce more collagen, a claim backed up by government studies and previous HuffPost reporting — if you like to know the research as much as we do. As Dr. Hannah Kopelman, a New York-based dermatologist, previously told HuffPost, collagen is a “structural protein” that “provides strength, elasticity and firmness” to the skin, i.e. the “qualities we associate with youthful, healthy skin.” Dr. Kopelman added that there is “some clinical data” suggesting that certain collagen peptides “can improve skin hydration, elasticity and texture over time, especially when combined with vitamin C, zinc or hyaluronic acid.”

Lucky for you, the gel included hyaluronic acid for extra hydration, as well as squalane oil for nourishment and glycerin to lock in the moisture and bounce. Fans say the gel offers amazing smoothing and firming, quickly.

“An amazing moisturizer with a visible wrinkle reduction after just a few days,” shopper A.Z. wrote. ”…I’ve noticed a real difference in the plumpness and smoothness of my skin after a few weeks of use,” another user wrote. “The peptides and collagen-boosting ingredients really do make my skin look firmer and more refreshed.”

The fragrance- and dye-free formula is gentle enough to be used twice a day, plays nicely under makeup and, according to fans, feels wayyyy more expensive than it is.

“This product rivals any 200-300 dollar cream,” one shopper said. “Goes on silky smooth, seems to plump almost immediately.” “It’s not that expensive and the results are amazing,” another wrote. “I normally don’t leave reviews, but Paula’s Choice is definitely a hidden skin care gem.”

Unlike thick, white creams, this translucent gel feels light on the face, with some even reporting a refreshingly cooling sensation when they apply it. Fans say they “immediately felt and saw the effects,” calling the gel “a great upgrade” from creams that “sit on skin” or are “slow to absorb.”

Fans also love the packaging, calling the pump dispenser “a big plus” that “keeps the product clean and makes it easy to dispense just the right amount.” Mainly, they love how versatile the gel is, giving their skin bounce, glow and all-day hydration.

Shopper Surfer Wife says the formula absorbs quickly, leaving skin “touchable,” even when layered with other products. ”…I like to store it in my beauty fridge,” they added. “It is so cooling on the skin and tames my redness.”

“I have dry, sensitive skin and the gel/cream formula is perfect for it,” Surfer Wife wrote. ”…I never feel like I’m drying out, even 12 hours after applying it. Most importantly, it does not pill under make-up. In fact, it seems to double as a primer. I have not used a primer since this was launched!”

Paula’s Choice plumping face moisturizer is the clear choice of fans looking for bounce and glow. Read more 5-star reviews and grab one on sale.

“I absolutely love this moisturizer! It feels lightweight but still very nourishing. My skin drinks it up without leaving any greasy residue, and I’ve noticed a real difference in the plumpness and smoothness of my skin after a few weeks of use. The peptides and collagen-boosting ingredients really do make my skin look firmer and more refreshed. The pump packaging is also a big plus—it keeps the product clean and makes it easy to dispense just the right amount. A little goes a long way, so even though it’s a bit pricey, it lasts longer than I expected. If you’re looking for something to hydrate and help with fine lines while giving your skin a healthy glow, this is worth every penny!” — Whit

Love the hybrid gel/cream texture and immediate absorption like a serum absent any residue. Plays well with other products. Skin looks firmer & feels terrific with no irritation (sensitive 57 yoa skin). This is a great upgrade from lotions or creams that may sit on skin or be slow to absorb. Love using this after derma-rolling!” — j a wagner

This product rivals any 200-300 dollar cream.. goes on silky smooth, seems to plump almost immediately. My skin has the look of bounce. It’s now my go too. I only use 1x a day and seems to be doing the job. My skin looks rested and refreshed.”Amazon customer

“This stuff is the best thing I have tried for a long time. Very helpful for wrinkles and dry skin. Has a nice long lasting plumbing effect.” — Amazon customer

The glow and plump of skin is incredible!! People have commented on my skin and been so impressed! I tell them it’s this lightweight magical potion. The price is on the higher side for me but you get what you pay for. You don’t need a lot just a pump.” — Jennifer

Looking for more solid skincare at solid prices? Check out these highly-rated favs for mature skin, courtesy of HuffPost Shopping.

Amazon

Good Molecules Yerba Mate wake up eye gel

If you’re an eye cream skeptic, then this affordable gel might change your mind. It’s made with caffeine, peptides and hyaluronic acid to help reduce the look of tired, puffy eyes and dark circles. The formula is surprisingly effective and can help perk up your peepers for just $6 a tube.

Promising review: “I really love this stuff. It is extremely moisturizing and feels great under your eyes. I am in my late 50’s and have had multiple coworkers ask me what I was doing differently the first week I started using it. It does seem to offer some lasting smoothing, hydrating and brightening effects, for me at least. I will definitely continue to use. For the price, it’s great and better than other more expensive brands I have tried. It also takes a very small amount to apply.” — LD16

Amazon

The Gold Bond Age Renew Crepe Corrector body lotion

Anti-aging skin care doesn’t stop at the neck; you can utilize powerful ingredients on the rest of your body as well. This incredibly popular crepe-correcting body lotion has a super-nourishing formula with powerful botanicals, anti-oxidants and omega fatty acids that can help to reduce the look of crepey, thin skin.

Promising review: “Pleasantly surprised. Really didn’t think this would work. I have been applying everyday for five days and have noticed an improvement in my skin. 100% recommend, don’t spend the money on the expensive products!” — Jill

Amazon

The CeraVe Skin Renewing Night Cream

Formulated with peptides, hyaluronic acid and ceramides, this CeraVe cream can help deeply hydrate the skin while helping to renew the skin’s natural barrier overnight. It’s ideal for dry winter months or for anyone who battles dry skin year-round. And the price point can’t be beaten.

Promising review: “I bought this based on a recommendation by a dermatologist. This was a budget buy due to its price point. I have dry, mature fair skin. I am really particular with the creams I put on my face. I can tell in 5 minutes if something is going to be hydrating enough for my skin. This CeraVe cream is a winner when it comes to moisturizing and hydrating your skin. It also has working benefits in it like peptide complex, niacinamide and ceramides. These all work for your skin. It is very hydrating, so I use it mainly at night. It has no fragrant smell. It does its job and is a good night cream. You will feel the difference.” — Michelle S.

The Real Deal: We use deal trackers and commerce experience to sift through “fake” hike-and-drop deals and other deceptive sales tactics. Products will usually be rated at least 4 stars with a minimum 15% discount. (And when there’s an exception, we’ll tell you why.)

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‘The Gold Standard’ For Anti-Frizz Hair Masks Is On Sale As We Speak

You may think that salon-looking hair demands going to the actual salon (and paying some premium prices.) Lucky for you, we spotted a collagen and argan oil hair mask from the brand Karseell, which reviewers deem “a five-star professional experience delivered in a jar,” especially in humid weather. The at-home mask is made with a blend of nourishing oils, proteins and herbal extracts to keep your strands silky smooth. It’s also currently on sale for 24% off, the lowest price it’s been in weeks — saving you some precious coins, too.

Reviewers say this creamy, dreamy mask “turns back the clock” on their strands, repairing damage they thought was permanent and making hair feel *Madonna voice* “like a virgin again…”

Teresita Rodriguez Bermùdez professes that it’s a “worth every penny” mask and far more than a conditioner; “it is a total hair transformation.”

“My hair went from being dry and brittle to feeling incredibly silky, hydrated and full of life,” they wrote, calling the mask “the gold standard” for high-end hair restoration treatments.

Made with an active collagen blend, wheat and soy proteins, shea butter, and chamomile extract — the coconut-scented mask is equal parts strengthening, soothing and shine-producing. (Note: The mask has wheat in it so it’s NOT gluten-free, for those with allergies and severe sensitivities.)

And it’s great for helping you combat humidity.

Warm, balmy weather is already here, and if your hair struggles in humidity — reviewers say this mask can help. “This was a game changer for my highlighted coarse hair,” one wrote. ”…My hair does not frizz up in humidity anymore!”

Another reviewer with keratin-treated hair, who’s used the mask for more than six months, says they love the way their hair feels, in all weather. ”[The mask] keeps it smooth and straight especially in humidity,” they wrote.

“I saw a video of a hairdresser using it and bought it to try,” another said. “It left my hair shiny and soft and helped with the frizz in severe humidity. You only have to use a little and the jar lasts a long time.”

It’s also incredibly easy to incorporate into your routine without over-complicating it.

Unlike lengthy, often noxious salon strengthening sessions, this at-home mask functions almost like a conditioner. Easily used in the shower, the mask can save you the time, effort and inconvenience of leaving home. The brand recommends applying it weekly to washed, towel-dried hair, spreading the mask from root to tip, letting it hang for 5-10 minutes and then rinsing. For a longer “mask” feel, some reviewers leave it on all night, “resulting in noticeably softer and smoother hair the next morning,” one said. Yet many reviewers report using it as they would a normal conditioner, for about 3 minutes while showering.

To make the container last longer and keep their routines quick, some reviewers say they mix the mask in with their normal conditioner for a little extra oomph. Another reviewer with type 3C natural hair used the mask before flat-ironing their hair. “My hair is frizz free, silky and has a salon look,” they wrote. “I will buy again. I’m hoping to be frizz free for at least a week.”

Like many brands, Karseell’s mask is designed for all hair types but unlike a lot of those — people with varying hair types and those with different hair challenges say this brought their hair back to life.

Those with menopause, hormonal changes, and general age-related hair changes vouch for the mask strengthening and restoring their strands.

″…One application and my hair is no longer dry and brittle,” a shopper in their 60s said. ”…It’s now soft and feels like it has life back in it!” A user almost 70 calls the mask “the greatest” they’ve ever found, noting it made their straw-like hair feel “like silk again.”

People with color- and chemically-treated hair, “dry and brittle” hair after going through chemo, those who use a lot of hot tools, or who just crave a “mirror-like” shine and frizz management.

It’s also loved by users for helping revive curls. One grandparent calls the mask “miracle in a jar,” for their 16-year-old grandson’s hair.

″…With the application of this product, detailing wasn’t bad and I could see his natural curl pattern shine through,” they wrote. ”…It was the first time in ages that I had seen his hair curl definition…”

Reviewers love this collagen and argan oil hair mask for keeping their strands smooth and strong, even in the heat. Read more 5-star reviews and take advantage of this great sale.

“This was a game changer for my highlighted coarse hair! It moisturizes so well, and smells great! I use it every third shampoo as a mask and a pea sized amount as a leave in on other shampoo days. Works even better when paired with the hair oil that comes with the set. My hair does not frizz up in humidity anymore!” — Amazon customer

“This product is very good. I felt like I went to the spa. I am a 67 year old female, with 3 inches below shoulder length, very dry and thinning hair. So opposite of what I used to have. I do not want to start cutting my hair short yet. I have tried dozens and dozens of products over the years. I can honestly say that Karseell hair treatment is by far, the best that I have used. Very easy to use. My hair feels and looks like I turned the clock back. My hair feels softer and more youthful. I only used it once so far, but what a difference. It’s a much try product.” — Amazon customer

My hair is straight, thin, and over-dyed for going on 3 decades. I skip hair trims. I like to use cheap hair dye & dry shampoo & heated tools. My hair usually goes up in a hair-clip as soon as I get up. Saying all that… this conditioner, after one use, made my hair feel like a virgin again… like super soft & shiny & with volume! I don’t understand the science of products and maybe this just coats my hair in a temporary silky substance, but it feels so good & I love it. I just put it on after shampooing & let it stay as long as I can find other things to do in the shower (so like 3 mins?) If one were to leave it on longer as the bottle suggests … holy moly… bet it’s amazing. It works for my hair.” — Jess

“This conditioner is absolutely amazing. I have very dry hair due to menopause and it’s left my hair smooth and glossy. I use it twice a week for best results.” —Brigitte Elzarki

HuffPost contributor Nishka Dhawan is a master at finding anti-frizz products for her naturally wavy hair. Check out more of her finds before the heat and the humidity really take over.

Amazon

A serum I’ve been using regularly that worked even in summer humidity

I’ve used this serum for the past few months, especially through the summer, and loved how it quickly smoothed my hair out without making it feel or look oily.

The serum itself is lightweight, vegan, and has a light coconut scent that won’t overwhelm your senses. It is also designed to increase shine and hydration in your locks, while keeping the frizz at bay for hours. Apply it to dry hair, starting at the hairline, and then tame any flyaways.

Promising review: “This serum tames frizz and flyaways without weighing my hair down. A little goes a long way and it leaves my hair silky and shiny, not oily.” — Stephanie Kanow

Amazon

An argan-oil based formula

OGX’s argan oil has over 15,000 reviews on Amazon and a 4.6-star rating. It’s lightweight, non-greasy, and is made to soften hair over time — even textured and colored hair. If you have dry tresses, this oil is made for you as it improves elasticity and adds shine with every use, according to the brand.

OGX’s Renewing Oil should leave you with stronger, healthier hair with regular use, and customers agree.

Promising review: “I’ve been using this argan oil for a few weeks, and it’s wonderful. It absorbs quickly without leaving a greasy residue and leaves my skin/hair feeling soft and nourished. The scent is mild and pleasant, and a little goes a long way.” — Darianny Campos Rodriguez

Amazon

A surprisingly weightless cream formula

This vegan cream-based formula is surprisingly weightless and offers up to 72 hours of frizz control. It has over 50,000 Amazon reviews and a 4.7-star rating, and for good reason.

It reduces frizz, protects your hair from humidity, acts as a heat protectant, and makes your hair easier to detangle, according to the brand. It also reduces blow-drying times. It’s made for all hair types, and is a great leave-in if you prefer to air-dry your locks.

Promising review: “My hair is fine, dense, and long. I purchased this on sale, not really expecting anything much because I had never used a styling creme. Now I use Olaplex No 6 every time I wash my hair! It makes my hair smooth, reduces frizz and helps my hair air dry a lot faster than without. My hair takes FOREVER to air dry without this product.” — Erica

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DNA solves 250-year-old mystery of the Seychelles’ lost crocodiles

For more than 250 years, stories from early explorers described crocodiles as a common sight along the shores of the Seychelles. But after permanent settlers arrived in 1770, the island population disappeared rapidly. Within about 50 years, the crocodiles had been completely exterminated.

Now, scientists have finally uncovered the true identity of these vanished reptiles through a new genetic analysis. The study found that the Seychelles crocodiles were not a separate species, as some once suspected. Instead, they were the westernmost known population of the saltwater crocodile (Crocodylus porosus), the world’s largest living reptile and one of its most capable ocean travelers.

DNA Reveals the Origins of Seychelles Crocodiles

Researchers from Germany and the Seychelles investigated the evolutionary history of the saltwater crocodile by comparing DNA from modern animals with genetic material taken from historical museum specimens. The team analyzed mitochondrial genomes from preserved crocodiles belonging to the genus Crocodylus, including rare samples from the Seychelles population that vanished roughly 200 years ago.

The findings confirmed an earlier theory that had been based only on the crocodiles’ physical appearance. Genetic evidence now shows the Seychelles animals were closely connected to saltwater crocodiles living thousands of kilometers away.

Crocodiles Crossed Vast Distances Across the Indian Ocean

Among all living crocodile species, the saltwater crocodile is especially well adapted for life at sea. Specialized salt glands allow these reptiles to remove excess salt from their bodies, enabling them to survive for long periods in seawater. Over time, this ability helped the species spread across enormous stretches of coastline and remote islands.

“The founders of the Seychelles population must have drifted at least 3,000 kilometers across the Indian Ocean to reach the remote archipelago, perhaps even much further,” says reptile expert Frank Glaw of the Bavarian State Collections of Natural History (SNSB) and senior author of the study.

Scientists believe these crocodiles likely traveled with ocean currents over generations, eventually establishing a population in the isolated islands of the Seychelles.

One of the World’s Most Wide Ranging Reptiles

“The genetic patterns suggest that saltwater crocodile populations remained connected over long periods and across great distances, pointing to the high mobility of this species,” explains first author Stefanie Agne of the University of Potsdam.

Today, the saltwater crocodile remains one of the most widely distributed reptiles on Earth. Before the Seychelles population was wiped out, the species occupied an even larger range that stretched more than 12,000 kilometers from Vanuatu in the Pacific Ocean to the Seychelles in the Indian Ocean.

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What in the World

Doctors are warning that some cancers are becoming more common in people in their 20s

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Can a rooftop garden help very ill patients heal faster?

Still in her hospital bed, connected to feeding tubes and life support, Hollie is the first patient to try out the new intensive care rooftop ward at King’s College Hospital in south London.

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Prostate cancer screening only for ‘a few thousand’ high risk men

Only men with a dangerous genetic variant and a family history of cancer should be offered screening, say UK advisors.

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Yes, Nails Can Turn Yellow From Age — This $24 Kit Helps Fix It

Believe it or not (you probably believe it), your nails are often one of the biggest indicators of your lifestyle and sometimes even your health. And if your precious fingers have assumed a yellow-ish tint these days — either due to aging, working the yard, or an affinity for back-to-back gel manicures that stain over time — we literally spotted a bright idea for that! Enter Londontown’s Mani Bright Nail Scrub, a whitening kit paste and a scrub brush designed to restore your nails back to their glory days. Even better, it’s only $24 for a salon-level transformation that can take a few years off your fingernails.

Whether it’s been months or years of yellowing, reviewers say this stuff can fix you right on up!

In case you didn’t know, yes, your nails can simply yellow with age or due to underlying health conditions like yellow nail syndrome, which typically affects folks 50 years or older.

“I’m almost 70 and I noticed my toenails were getting a tinge of yellow,” one shopper wrote of their natural manicure experience. “So I tried this stuff in the shower and it worked really well.”

“My nails looked young again, without any yellowish tone,” another reviewer, Tallulah Belle, vouched.

Known for its $20 milky nail concealer that helps conceal your imperfections underneath a shockingly natural sheen (HuffPosters LOVE IT), Londontown’s Mani Bright nail kit is designed to remove the color issue altogether. Easy to use, it’s a mere two-step restoration process that involves the scrub solution and a brush. The scrub formula features calcium carbonate to remove the odd colors, sodium bicarbonate to boost whitening plus citrus extract to naturally brighten.

Of course, age isn’t the only reason your nails could stand some brightening care.

“This is a definite YES!” another reviewer wrote. “So easy and works GREAT! Nail polish had my nails looking dull and yellowing and now they are great even after the first use! I will definitely continue purchasing this one!”

Results are so impressive, it leaves reviewers wishing they had documented their journey using the brightening kit sooner. “Whoa, this stuff really works,” says one thrilled user. “I wish I had taken a photo before and after. I didn’t think about it till after I used it. My nails look so white and bright. Very impressed with this product…”

Of the lot who adore this nail cleaning and brightening kit, we’re most pleasantly surprised by the number of gardeners who credit it with transforming nails that undergo routine manhandling.

“This is so handy,” one card-carrying green thumb holder, Lori, shared. “Even though I wear garden gloves I like to scrub my nails after gardening. Perfect!”

“Nice and compact,” another reviewer shared. “Can put in a travel bag for convenience of use. Especially great for hands and nails after gardening. The shape is perfect with the cleaning soap to get under nails and into the crevices of nail beds for a clean job.”

And it’s not just gardeners who benefit: it’s for folks who tend to get messy in the kitchen or seem to use their hands for a range of DIY purposes (basically, a significant chunk of the population). “It sure does whiten the ends of your nails,” says one pleased shopper. “The underneath of my nails are stained from picking weeds in the garden, cooking, etc., (mustard REALLY stains them), and generally speaking using my fingernails as screwdrivers. I used this product one time, scrubbing the underneath of my nails with the brush and the difference was amazing.”

“Best analogy is like going to a dentist and getting a professional teeth cleaning. The results were night & day,” another shopper wrote.

Now that’s worth every penny.

Check out more promising reviews of this nail brightening kit below.

I’m almost 70 and I noticed my toenails were getting a tinge of yellow. So I tried this stuff in the shower and it worked really well.”Ron

“I have been using this product for almost two weeks and I see so much of a difference in my nails. My nails look so much brighter and cleaner now since I have been using the scrub. I am so glad I discovered this product and would recommend this to anyone! Definitely worth the hype!Yana H.

“I wasn’t sure what to expect, but this stuff actually does work! My nails were kind of yellow and lackluster, particularly at the tips, and one use made them look much cleaner and brighter. The brush that comes with it makes it easy to reach in to the tiny edges, and it didn’t dry out my nails like I feared it might. Such a nice feeling to use—definitely adding it to my routine.”Cassidy V.

“I loved this nail brush and cleansing cream. I bought more for gifts.”Patty

“Exceeded my expectations. My nails were stained from polish and this product worked wonderfully. The included brush is of nice quality as well.”Whispering willow

The Real Deal: We use deal trackers and commerce experience to sift through “fake” hike-and-drop deals and other deceptive sales tactics. Products will usually be rated at least 4 stars with a minimum 15% discount. (And when there’s an exception, we’ll tell you why.)

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Why the gut is known as the second brain

Your gut doesn’t just respond to your brain – it helps shape your emotions. Professor of Biomolecular Medicine Jon Swann explains why.

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Cynthia Erivo Says ‘Bodyguard’ Jokes After Wicked Premiere Incident Were Rooted In Racism

Cynthia Erivo is reflecting on the fall-out from an incident that took place at the premiere of the second Wicked film in Singapore last year.

In November 2025, Cynthia and her co-star Ariana Grande were attending the Wicked: For Good premiere when a man leapt over a barrier and grabbed the No Tears Left To Cry singer, before jumping up and down.

Viral footage of the incident showed the British performer stepping in to protect her co-star, which inspired jokes and memes referring to her as Ariana’s “bodyguard”.

However, in a new interview with Variety, Cynthia suggested that these jokes were evidence that society has not yet “come to terms with the insidious nature of how we view Black women”.

“I’m sure people will read this and think, ‘Oh, for goodness’ sake, it’s not about that.’ But it is,” she said.

Cynthia continued: “That’s what was being made fun of. It was my physique; it was my shape; it was the fact that I was bald; it was about what I looked like. And because of that, there was this assumption that I was bigger than my co-star and so I had to be controlling or protecting, and that was my role.

“I would hazard a guess that it would not have been the same had it been the other way around.”

Cynthia Erivo
Cynthia Erivo

via Associated Press

Later in the interview, Cynthia claimed that the incident in Singapore put her off campaigning for an Oscar for her work in Wicked: For Good.

She lamented: “I just felt like my humanity had been bastardised. I felt like something I did instinctively had been made to be something that it simply was not because of the way people see women who look like me, and because of the assumptions that are made, and I just didn’t want to be a part of that, really and truly.”

Cynthia added that people’s preconceptions about the second Wicked film being inferior to the first contributed to her not wanting to campaign for an Oscar.

In the end, Wicked: For Good was completely snubbed at the 2026 Oscars, despite the first film receiving 10 nominations (and two wins) a year earlier.

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Researchers block key protein that helps Parkinson’s spread through the brain

Researchers at the Perelman School of Medicine at the University of Pennsylvania have identified a brain immune protein that may play a major role in the progression of Parkinson’s disease (PD). Their findings, published in Neuron, suggest that blocking this protein with monoclonal antibodies could eventually lead to treatments that slow the disease in its earliest stages.

The protein, known as glycoprotein nonmetastatic melanoma B (GPNMB), appears to help harmful Parkinson’s-related damage spread from one brain cell to another. Scientists say targeting it may offer a new strategy for slowing the worsening of the disease over time.

“Many patients with Parkinson’s disease are diagnosed in the early stages, when symptoms are relatively mild, but there is currently no treatment that slows the progression,” said lead author, Alice Chen-Plotkin, MD, Parker Family Professor of Neurology. “These early results are a promising step towards developing this type of treatment.”

How Parkinson’s Disease Spreads in the Brain

Parkinson’s disease affects more than one million Americans, and approximately 90,000 people in the United States are diagnosed each year. Although researchers still do not fully understand what causes the disease, scientists have known for years that it gradually spreads through the brain in stages.

A protein called alpha-synuclein is central to this process. In Parkinson’s disease, alpha-synuclein forms abnormal clumps inside neurons. These clumps damage the affected cells and can then move into nearby healthy neurons, where they continue spreading.

As more areas of the brain become affected, symptoms worsen. Patients may develop tremors, difficulty walking, balance problems, and trouble swallowing.

Current treatments, including levodopa and deep-brain stimulation, can help reduce symptoms. However, no approved therapy has been shown to slow or stop the underlying progression of Parkinson’s disease itself.

Brain Immune Cells May Help Fuel Disease Progression

In earlier research published in 2022, Chen-Plotkin and colleagues identified GPNMB as an important molecule involved in the spread of alpha-synuclein between neurons. That discovery made the protein a promising target for future therapies.

In the new study, the research team found that microglia, the brain’s immune cells, are a major source of GPNMB in Parkinson’s disease. When neurons become damaged or begin dying, nearby microglia respond by producing larger amounts of the protein.

Enzymes then cut part of GPNMB away from the cell surface, allowing it to move freely between cells in the brain.

Using preclinical laboratory experiments with cultured neurons, researchers developed antibodies designed to block GPNMB. The antibodies successfully prevented alpha-synuclein pathology from spreading from one cell to another.

“These results suggest Parkinson’s disease may be driven by a self reinforcing cycle — alpha-synuclein accumulates in neurons, damaging the neurons. The injury to the neurons initiates the release of GPNMB, which accelerates the spread of alpha-synuclein, leading to further damage,” Chen-Plotkin said. “Interrupting this cycle would hopefully slow, or even stop, the spread of alpha-synuclein through the brain and the neurodegeneration that follows.”

Human Brain Analysis Supports the Findings

To examine whether the results were relevant in people, researchers analyzed tissue samples from 1,675 brains stored in the Penn Brain Bank.

The team found that individuals carrying genetic variants linked to higher GPNMB production also showed more extensive alpha-synuclein pathology. According to the researchers, this provides strong evidence that GPNMB plays a significant role in the progression of Parkinson’s disease in humans.

Importantly, elevated GPNMB levels were not connected to markers associated with other neurodegenerative conditions, including Alzheimer’s disease.

“These results are promising for laboratory models and human brain tissue analysis, but we still have a lot of work to do before we can translate this therapy into humans,” said Chen-Plotkin. “That being said, these results are encouraging as we continue to work towards a novel treatment for PD.”

The study received support from the National Institutes of Health (R37 NS115139, P30 AG010124, U19 AG062418, P01 AG084497), SPARK-NS, the Parker Family Chair, and the Lipman Family Fund.

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