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
05/01/2027
Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...
04/08/2026
Dalet, a leading technology and service provider for media-rich organizations, t...
04/07/2026
April 7 2026, 19:00 (PDT) Detective Conan: Fallen Angel of the Highway Opens in...
01/06/2026
January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026
Throughout the week, Dolby brings to life the latest innovatio...
13/05/2026
New Adobe Premiere Color Grading Mode Accelerated on NVIDIA GPUs
Joel Pennington May 13, 2026
0 Comments
New NVIDIA RTX-accelerated features streamlin...
13/05/2026
Grass Valley announced that dB Broadcast has delivered new IP-based outside broadcast (OB) trucks for Cloudbass, featuring Grass Valley LDX 100 Series cameras a...
13/05/2026
Ikegami will exhibit the latest additions to its wide range of broadcast production cameras, control units, viewfinders and monitors on stand 5D3-1 at Broadcast...
13/05/2026
FISE, working with the founding members of the XR Sports Alliance (XRSA), Accedo, Qualcomm Technologies, Inc. and HBS, have collaborated to develop an immersive...
13/05/2026
Canon Unveils New EOS R6 V Full-Frame EOS Camera and RF20-50mm F4 L IS USM PZ Bu...
13/05/2026
Boston Conservatory at Berklee Honors Beth Morrison and Moses Pendleton at Comme...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
13/05/2026
Creative software developer Foundry today announced the latest developments on Nuke Stage. A purpose-built application for end-to-end virtual production and in-...
13/05/2026
A definitive portrait of one of Ireland's most influential musicians
New TV documentary airs Monday 18 May on RT One and RT Player at 9.35pm
Watch the...
13/05/2026
Agentic AI is changing the way users get work done. Following the success of OpenClaw, the community is embracing new open source agentic frameworks. The latest...
13/05/2026
Reinforcement-learning agents - AI systems that learn by trial and error - can c...
12/05/2026
Beyond the Hype: A Strategic Post-Hoc Analysis of NAB 2026 If NAB Show 2026 had an underlying theme, it was a quiet, industry-wide pivot from the high-energy sp...
12/05/2026
Guntermann and Drunck (G&D), a Panoptec Technologies Group company, and CT Square, led by Chandresh Shah, have announced a joint venture to distribute G&D and V...
12/05/2026
With 30 days until the start of the FIFA World Cup 2026, Telemundo, the exclusive Spanish-language home of the tournament in the United States, has announced th...
12/05/2026
The NHL has announced the return of Stanley Pup for its third consecutive year, a 90-minute special featuring adoptable rescue dogs competing on a miniature rin...
12/05/2026
NBCUniversal presented its 2026 Upfront to advertisers at Radio City Music Hall, detailing upcoming programming across NBC, Peacock, Bravo, and Versant properti...
12/05/2026
FOX Sports has announced funding for the Fandom and Social Connection Initiative at Harvard Kennedy School's Shorenstein Center on Media, Politics, and Publ...
12/05/2026
TNDV and Live Media, both divisions of Live Media Group, supported live broadcast coverage around NCAA Final Four weekend in Indianapolis, including the March M...
12/05/2026
The European Football Alliance (EFA) has announced a content distribution agreement with Fubo Sports Network, the free ad-supported streaming TV (FAST) channel ...
12/05/2026
For the first time, Spanish-speaking fans in the U.S. will have two separate tel...
12/05/2026
CP Communications led a comprehensive spectrum management initiative on behalf of Churchill Downs during Kentucky Derby week, coordinating RF assets across the ...
12/05/2026
LiveU has announced a strategic partnership with DRONERESPONDERS, a 501(c)3 non-...
12/05/2026
Open Broadcast Systems has announced that BMC TV, a specialist in IP transport of broadcast content, has selected the Open Broadcast Systems 5G Flyaway solution...
12/05/2026
NEP Europe, part of NEP Group, has announced it will deliver broadcast solutions...
12/05/2026
Grass Valley has announced continued collaboration with Ravensbourne University ...
12/05/2026
Stats Perform has announced the launch of Opta Pulse, an AI-assisted video creation and distribution platform for leagues, rights holders, and broadcasters. The...
12/05/2026
FOX Sports has announced a collaboration with Sesame Workshop to integrate Sesame Street characters into FOX Sports' FIFA World Cup 2026 programming. Conten...
12/05/2026
To date, NHL Productions has produced 19 broadcasts with commentary in American Sign Language
NHL in ASL (American Sign Language) may be just one show, but the...
12/05/2026
Google's Brian Albert: creators, athletes, highlights, nostalgia, second-scr...
12/05/2026
A still from Past Lives by Celine Song, an official selection of the Premieres program at the 2023 Sundance Film Festival. (Courtesy of Sundance Institute | p...
12/05/2026
Spotify is where fans and artists come together, turning discovery into somethin...
12/05/2026
Features patented Marco-MMC clocking technology
Black Lion Audio's latest release combines the company's expertise in clocking with their renowned p...
12/05/2026
New Track Panel, sequencer upgrades & more
Following their recent public beta release, Reason Studios have announced the full release of Reason 14. With the...
12/05/2026
One month to go! SBS reveals expansive FIFA World Cup 2026 lineup beyond the pi...
12/05/2026
Rohde & Schwarz presents its advanced solutions for power electronics testing at...
12/05/2026
aconnic AG (ISIN: DE000A0LBKW6), Munich, has developed a modified fund raising p...
12/05/2026
Share
Copy link
Facebook
X
Linkedin
Bluesky
Email...
12/05/2026
Tyrell Corporation, specialists in high-end live sports and entertainment broadcasts, was tasked with delivering compelling broadcast coverage of premier equest...
12/05/2026
Registration is now open for IBC2026 as the global media, entertainment and technology community prepares to converge on the RAI Amsterdam from 11 14 September ...
12/05/2026
Ross Video, a global leader in live video production technology, will present its latest innovations and integrated production workflows at BroadcastAsia 2026, ...
12/05/2026
500 selected leaders from around the world across start-ups, corporates, and venture capital. Over 50bn in assets under management among attending investors, a...
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. 
