Hidden network of enzymes accounts for loss of brain synapses in Alzheimer's The discovery of abnormal chemical reactions may lead to novel targets for drugs that treat neurodegenerative diseases.
December 03, 2020
LA JOLLA, CA A new study on Alzheimer's disease by Scripps Research scientists has revealed a previously unknown biochemical cascade in the brain that leads to the destruction of synapses, the connections between nerve cells that are responsible for memory and cognition.
The findings present a fresh angle for discovering drugs that treat Alzheimer's disease, which affects roughly 50 million people worldwide. The study, led by Scripps Research Professor and Step Family Foundation Endowed Chair Stuart Lipton, MD, PhD, appears in the journal Science.
This newly-discovered series of abnormal chemical events, termed protein transnitrosylation reactions, contribute to synapse loss, the main driver of memory loss and cognitive decline in Alzheimer's.
Lipton, who is also a clinical neurologist, explains that most recent attempts to develop Alzheimer's treatments have targeted the sticky protein known as beta amyloid that accumulates in the brain of patients, disrupting cell communication and causing inflammation. However, for a variety of reasons, these attempts have failed in clinical trials.
This work gives us new hope for better therapeutic targets, as the reactions we discovered are downstream of amyloid action, Lipton says. We've opened up a whole new avenue for drug development.
Lipton is no stranger to drug development for Alzheimer's and Parkinson's diseases. Drugs developed in and patented by his laboratory have led to four FDA-approved medicines for these diseases, including the widely prescribed drug, memantine (Namenda ). Much better drugs are needed, however, Lipton says.
A chemistry success story
In the new study, Lipton and his team used physical chemistry techniques to quantify how electrons participate in chemical reactions, as they suspected unknown processes may be taking place in the brain. Through this, they uncovered the entirely new series of biochemical events in nerve cells affected by Alzheimer's.
They found that small clumps of beta amyloid protein trigger excessive neuron activity and inflammation, leading to the destructive series of transnitrosylation reactions.
The process begins with excessive levels of nitrogen (N) and oxygen (O) atoms joining together as an NO group, which is then transferred to a protein building block called cysteine to regulate the activity of the protein. A series of these aberrant protein reactions cuts off energy to the brain's nerve cells by disrupting their mitochondria organelles that generate power for the cell's biochemical reactions. This eventually leads to loss of synapses connecting the nerve cells.
We were able to show that these reactions occur in brains of Alzheimer's patients, and when we prevented these reactions in the brains of animal models of the disease, we protected the synapses, Lipton says. Our findings suggest that it may be possible to intercede to reverse synapse damage in spite of plaques and tangles, he added, referring to plaques of beta amyloid and tangles of misfolded tau protein, both of which are characteristic of Alzheimer's disease.
He notes that while normal levels of NO foster memory and learning, excessive levels can build up as we age and become harmful to synapses.
With this new knowledge, we may be able to restore synaptic connections in Alzheimer's patients after extensive plaques and tangles have formed in their brains, adds Tomohiro Nakamura, PhD, senior staff scientist in the Lipton laboratory group and first author of the study.
Revealing secret connections
Lipton says that one of the team's most incredible findings was that the three enzymes discovered to pass NO to each other along a concerted chain of events, resulting in energy failure, were previously not thought to be even remotely related to one another. Each of the enzymes is important in its own right in a completely disparate normal biochemical pathway, and yet they interact under disease conditions in a novel manner to trigger intense neuronal stress and synapse damage.
This type of hidden or ghost' pathway may only become evident under disease conditions and may represent an important fundamental tenet of why we did not understand the disease process previously, Lipton says. If we do not know about a pathway, scientists cannot study its contribution to disease or develop drugs to treat it.
While many molecular biochemical pathways have been discovered, an over-reliance on this existing body of evidence can actually impede discovery of disease processes, he adds.
Hence, the most important aspect of the work is that we have to be on our guard to look for new pathways and new relationships of existing enzymes in order to understand and treat neurodegenerative disorders such as Alzheimer's, Lipton says.
In addition to Nakamura and Lipton, other authors of Non-canonical transnitrosylation network contributes to synapse loss in Alzheimer's disease, include Chang-ki Oh, Xu Zhang, Kevin Lopez, Amanda Deal, Henry Scott, Lujian Liao and John R. Yates III from Scripps Research; and Daniel Gibbs, Brian Spencer, Robert Rissman and Eliezer Masliah from the University of California, San Diego.
The work was funded by the National Institutes of Health and philanthropic support.
Neurological Disorders Molecular and Cellular Biology Lipton, Stuart
Most recent headlines
11/12/2025
Dalet, a leading provider of cloud-native, end-to-end media workflow solutions, ...
27/11/2025
LONDON Vizrt has added several AI-driven advanced features offering improved speed, intelligence and accuracy in the newest version of its media asset managemen...
27/11/2025
Prime Video has launched AI-powered video season recaps in a beta version for select English-language Prime Original series in the U.S., a move Amazon is callin...
27/11/2025
27 Nov 2025
GSMA brings M360 Eurasia 2026 to Samarkand in partnership with VEON...
27/11/2025
Tahar Rahim and Izuka Hoyle star in the gripping six-part Sky Original from Acad...
27/11/2025
Thursday 27 November 2025
Sky Arts Reveals the Nation's Greatest Basslines - and Queen Reign Supreme
The UK's most iconic basslines have been revealed...
27/11/2025
Back to All News
Stranger Things 5': Prepare for One Last Adventure With O...
27/11/2025
The media industry has a paradox at its core. It's an industry built on light, color and imagination, yet behind the scenes, it's powered by one of the ...
27/11/2025
Rating reflects rating progress across areas including policies, diversity & inclusion, health & safety and Net Zero leadership
Winchester, UK, 27 November 202...
27/11/2025
What are the industry standards for Retail Media? Kathryn explains that certification is based on the IAB Europe Retail Media Measurement Standards and the IAB ...
27/11/2025
World champion boxer and Irish sporting icon Katie Taylor will be in studio this...
27/11/2025
Roblox, one of the world's most popular online gaming platforms for primary ...
27/11/2025
Black Friday is leveling up. Get ready to score one of the biggest deals of the season - 50% off the first three months of a new GeForce NOW Ultimate membership...
26/11/2025
SVG Sit-Down: Prime Video EP Mike Muriano Previews Massive Black Friday Slate Fe...
26/11/2025
A cinematic snow sculpture at the 1995 Sundance Film Festival. Photo by Randall Michelson...
26/11/2025
Book podcasts are booming. On Spotify, you'll find everything from celebrity book clubs to deep dives with bestselling authors. And in markets where audiobo...
26/11/2025
Mumbai, November 24, 2025: In a first-of-its-kind initiative, JioStar, in collab...
26/11/2025
LONDON Factual content producer ITN Productions has launched a new low-latency IP gallery for news bulletins....
26/11/2025
MIAMI TelevisaUnivision said it struck a new multiyear distribution agreement with YouTube TV that includes distribution of TelevisaUnivision's U.S. network...
26/11/2025
OpenDrives, Inc., a leader in software-defined data storage and data services, today announced the launch of the Atlas Corporate Creative Solution. This new Atl...
26/11/2025
Disguise, the industry-leading company powering the world's biggest live performances, is partnering with pioneering LED wall manufacturer DVS to give atten...
26/11/2025
HighField AI, the pioneer in agentic and multimodal automation for broadcast and media production, today announced the expansion of its global channel partner n...
26/11/2025
As high-stakes Premier League fixtures approach and additional premium content launches, with MONO positioning themselves to dominate Thailand's sports stre...
26/11/2025
Hosting a wide variety of events from high-intensity NHL games to complex live music concerts and major entertainment productions, Montreal's 21,000 capacit...
26/11/2025
Vizrt, the leader in live production technology revolutionizing viewer engagement and experience, releases AI-driven advances focusing on speed, intelligence, a...
26/11/2025
ITN Productions, an award-winning factual content producer, today launched a new low-latency IP gallery for news bulletins. Responsible for delivering a leading...
26/11/2025
Ikegami reports ongoing advances throughout 2025 in developing and delivering coordinated television production solutions that maximize quality, versatility and...
26/11/2025
Following the Nov. 21 blackout of NBCUniversal channels on Fubo, the two sides have traded barbs about their inability to reach a new carriage deal....
26/11/2025
LONDON As TV sports rights become increasingly important for both broadcasters and streamers, Ampere Analysis predicts global investment in the genre will surpa...
26/11/2025
LOS ANGELES Vubiquity said it has achieved the Amazon Web Services (AWS) Media & Entertainment Competency as part of the AWS Partner Network (APN). This designa...
26/11/2025
WASHINGTON The Federal Communications Commission's Enforcement Bureau said it has entered into a consent decree with Comcast calling for the cable company t...
26/11/2025
Berklee Named to the Hollywood Reporters Top Music Schools List The publication highlights the college's screen scoring program, industry partnerships, and ...
26/11/2025
Back to All News
Animated Series Love Through a Prism' Casts New Light on ...
26/11/2025
Back to All News
NALIP Unveils Fifth Cohort of Director Incubator
Social Impact
26 November 2025
United States
Link copied to clipboard
The National Assoc...
26/11/2025
YouView Achieves Greenly Gold Certification for SustainabilityNov 26, 2025
YouView is proud to announce a Gold Certification award from Greenly for our perform...
26/11/2025
Back to All News
Netflix Deepens Partnership with Taiwan's 62nd Golden Hors...
25/11/2025
Tracy Bonareri Onchoke, an investigative journalist from Kenya is the winner of the Thomson Foundation's Young Journalist Award 2025.
The 26-year-old-sele...
25/11/2025
SVG All-Stars: Blayke Scheer, Senior Director, Creative Content, YES NetworkThe Indiana alum has turned storytelling into an artform for more than two decadesBy...
25/11/2025
Op-Ed: With FCC's C-Band Auction on the Horizon, Broadcasters Need Proven, C...
25/11/2025
Analysis: Is Baller League really the future of sport? By Callum McCarthy, Editor-at-Large
Tuesday, November 25, 2025 - 10:10
Print This Story
With KSI on...
25/11/2025
Platinum Whitepaper: The Growth of Broadcast in the World of Major Large Scale E...
25/11/2025
SVG Summit 2025 Preview: SVG Women's Sports WorkshopBy Samantha Gabay
Tuesday, November 25, 2025 - 10:27 am
Print This Story | Subscribe
Story Highlig...
25/11/2025
SVG New Sponsor Spotlight: CacheFly's Matt Levine on the Evolving Role of th...
25/11/2025
Peacock's EA SPORTS Madden NFL Cast Levels Up on Thanksgiving With SkyCam as...
25/11/2025
Mathias Broe attends the 2025 Sundance Film Festival premiere of Sauna at Library Center Theatre. (Photo by Michael Hurcomb/Shutterstock for Sundance Film Fes...
25/11/2025
The best playlists, podcasts, and audiobooks bring a little extra magic to your daily routine. With new features and offerings, Spotify Premium delivers even mo...
25/11/2025
Comprehensive new research confirms what we already knew: Australian music fans love the quality, quantity, and access they have to new and local music on strea...
25/11/2025
Applicable Products
Objectives The purpose of this application note is to give a brief background on 5G (NR) wireless communication an explain the reason a SN...
25/11/2025
Nielsen will now measure both Lionsgate's FAST channel MovieSphere and Movie...
Hidden network of enzymes accounts for loss of brain synapses in Alzheimer's The discovery of abnormal chemical reactions may lead to novel targets for drugs that treat neurodegenerative diseases. 
