Researchers have identified the protein TRIM11 as a potential new therapeutic target for Alzheimer’s disease. This protein has been observed to prevent neurodegeneration and enhance cognitive and motor performance in animal experiments similar to Alzheimer’s. The protein TRIM11 appears to be instrumental in clearing detrimental protein accumulations associated with neurodegenerative conditions.
The concentration of TRIM11 protein was observed to decrease in Alzheimer’s disease models, based on novel research from Penn Medicine. This hints that rejuvenating this protein might ameliorate cognitive and motor function.
Fresh research from the Perelman School of Medicine at the University of Pennsylvania revealed that a gene that produces a protein related to tau protein production—TRIM11—was observed to prevent decay in small animal models resembling neurodegenerative diseases akin to Alzheimer’s disease (AD), whilst enhancing cognitive and motor capabilities.
Furthermore, the research acknowledged TRIM11 as a key player in clearing protein tangles causing neurodegenerative diseases such as AD. The recent findings were published in the scientific journal, Science.
AD is the most prevalent cause of dementia among the elderly population, affecting an estimated 6 million Americans.
It is a progressive neurological disorder that gradually erodes memory and cognitive abilities. Pioneering research led by Virginia M.Y. Lee, Ph.D., and the late John Q. Trojanowski, MD, Ph.D., at Penn Medicine suggests that neurofibrillary tangles (NFTs) of tau proteins, causing neuronal death, are one of the fundamental causes of neurodegenerative diseases, leading to AD symptoms such as memory loss.
In AD patients, tau protein tangles (NFTs) are increased, but TRIM11 is decreased. These tau protein tangles are also linked with over 20 other dementias and movement disorders, known collectively as tauopathies. Yet, the reasons for the aggregation of tau proteins and formation of NFTs in these diseases are not well-understood, making it challenging to develop effective therapies.
“Protein quality control systems in most organisms eliminate faulty proteins and prevent the formation of tangles. However, it was unclear how this process operates in humans, or why it fails in certain individuals,” stated senior author Xiaolu Yang, Ph.D., a professor of Cancer Biology at Penn. “Now, we have identified the gene controlling tau function, presenting a promising target for developing treatments for AD and related disorders.”
Yang’s team, including first author Zi-Yang Zhang, Ph.D., had earlier discovered that TRIM proteins are crucial in protein quality control in animal cells. Among more than 70 human TRIMs, they found that TRIM11 is a key player in inhibiting tau aggregation. TRIM11 functions in three ways: binding to tau proteins and aiding in their elimination, acting as a ‘chaperone’ to prevent tau protein misfolding, and dissolving existing tau aggregates.
These findings were validated using postmortem brain tissues from 23 individuals with AD and 14 healthy controls. Researchers discovered that TRIM11 protein levels are significantly lower in AD patients compared to healthy individuals.
To assess the therapeutic potential of TRIM11, scientists used gene therapy to introduce the TRIM11 gene into multiple mouse models. They found that mice with tau pathologies that received the TRIM11 gene showed a significant reduction in NFT development and accumulation, with marked improvements in cognitive and motor abilities.
Yang stated, “These findings suggest that TRIM11 could play a crucial role in protecting individuals from Alzheimer’s and similar diseases. We also found potential for future therapies that restore TRIM11 in individuals with lower levels. We look forward to collaborating with our colleagues to explore the possibility of developing gene therapies that halt the progression of neurodegenerative disease.”
This study was sponsored by the National Institutes of Health and funding received by Penn under a sponsored research agreement with Wealth Strategy Holding Limited. Yang has affiliations with patents and patent applications related to TRIM proteins, and is a co-founder and equity holder of Evergreen Therapeutics LLC, which received investments from Wealth Strategy Holding Limited.
Table of Contents
Frequently Asked Questions (FAQs) about Alzheimer’s Disease Treatment
What is the key finding of the new Alzheimer’s disease research?
The study identified the protein TRIM11 as a promising new target for the treatment of Alzheimer’s disease. This protein is found to inhibit neurodegeneration and improve cognitive and motor functions in animal models resembling Alzheimer’s.
Why is TRIM11 significant in the context of Alzheimer’s disease?
TRIM11 plays a crucial role in eliminating harmful protein tangles associated with neurodegenerative diseases like Alzheimer’s. The levels of TRIM11 are found to be reduced in models of Alzheimer’s disease, suggesting that restoring this protein could potentially improve cognitive and motor functions.
What are the key functions of TRIM11 protein in relation to tau proteins?
TRIM11 has three primary functions in relation to tau proteins: it binds to tau proteins, especially the disease-causing mutant variants, and aids in their elimination; it acts as a “chaperone” to prevent tau proteins from misfolding; and it dissolves existing tau aggregates.
How was the role of TRIM11 investigated in the study?
The researchers used gene therapy to introduce the TRIM11 gene into multiple mouse models with tau pathologies. The mice that received the TRIM11 gene showed a significant decrease in the development and accumulation of neurofibrillary tangles and demonstrated improved cognitive and motor abilities.
What is the future implication of this research?
The research suggests the possibility of developing gene therapies that increase levels of TRIM11 to halt the progression of neurodegenerative diseases like Alzheimer’s. It opens up a new potential pathway for the development of effective treatments for Alzheimer’s and related disorders.
More about Alzheimer’s Disease Treatment
- Penn Medicine
- Perelman School of Medicine at the University of Pennsylvania
- National Institutes of Health
- Science Journal
- Evergreen Therapeutics LLC
- Alzheimer’s Disease Information
- Neurodegenerative Diseases Information
