Goo news!
"... Now, scientists have identified an enzyme that appears to stem amyloid at its source.
Previous research has demonstrated that SIRT6, which belongs to the sirtuin family of proteins, plays a role in multiple cellular processes related to aging and longevity. Some people who have lived to the age of 100 or more possess a rare variant of the gene that codes for this protein, which boosts DNA repair in human cells. In one study, male mice genetically modified to produce excess SIRT6 had significantly longer lifespans than their unmodified peers.
In this new study, researchers report that this so-called “longevity protein” trims key chemical groups from amyloid precursor protein (APP), marking it for destruction and preventing it from forming damaging plaques. Mice designed to model Alzheimer’s have less SIRT6 and more APP, researchers found. When the scientists activated SIRT6 in these rodents’ brains, however, they ended up with fewer plaques, healthier neurons, and displayed improved cognitive functioning—suggesting that the enzyme could be a promising target for the treatment of Alzheimer’s disease."
From the editor's summary and abstract:
"Editor’s summary
... Cheng et al. mechanistically link these phenomena by showing that SIRT6 deacetylated the amyloid precursor protein (APP) to promote its degradation. Treating aged mice and Alzheimer’s disease model mice with a chemical activator of SIRT6 reduced amyloid plaque burden, preserved neurons, and improved cognitive performance. The findings suggest that pharmacological activators of SIRT6 may ameliorate amyloid-associated pathology and symptoms in patients. ...
Abstract
Alzheimer’s disease (AD) is an aging-related neurodegenerative disorder that results in progressively impaired memory and is often associated with amyloid plaques. Previous studies implicate the deacetylases SIRT1 and SIRT2 in regulating the processing of amyloid precursor protein (APP). Here, we investigated whether APP is regulated by the related deacetylase SIRT6, which shows aging-associated decreases in activity. We found that the abundance of SIRT6 was reduced in the cortex and hippocampus of aged and AD model mice and negatively correlated with that of APP. In mouse hippocampal neurons and transfected human cells, SIRT6 interacted with and deacetylated APP at three consecutive Lys residues (Lys649, Lys650, and Lys651). This deacetylation, in turn, increased the ubiquitylation of APP, leading to its proteasomal degradation. SIRT6 abundance in neurons was reduced by oxidative stress and DNA damage, both of which are implicated in neurodegenerative pathology. Systemic pharmacological activation of SIRT6 ameliorated both amyloid pathology and cognitive deficits in APP/PS1 mice, a mouse model of AD. The findings demonstrate that the activity of SIRT6 destabilizes APP and suggest that activating SIRT6 has therapeutic potential to reduce amyloid-associated pathology in patients with AD."
No comments:
Post a Comment