mTOR IN DOWN SYNDROME: ROLE in A ß and TAU NEUROPATHOLOGY and TRANSITION to ALZHEIMER DISEASE-LIKE DEMENTIA.

mTOR IN DOWN SYNDROME: ROLE in Aß and TAU NEUROPATHOLOGY and TRANSITION to ALZHEIMER DISEASE-LIKE DEMENTIA. Free Radic Biol Med. 2017 Aug 11;: Authors: Di Domenico F, Tramutola A, Foppoli C, Head E, Perluigi M, Butterfield DA Abstract The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase involved in the regulation of protein synthesis and degradation, longevity and cytoskeletal formation. The mTOR pathway represents a key growth and survival pathway involved in several diseases such as cancer, obesity, cardiovascular disease and neurodegenerative diseases. Numerous studies linked the alterations of mTOR pathway to age-dependent cognitive decline, pathogenesis of Alzheimer disease (AD) and AD-like dementia in Down syndrome (DS). DS is the most frequent chromosomal abnormality that causes intellectual disability. The neuropathology of AD in DS is complex and involves impaired mitochondrial function, defects in neurogenesis, increased oxidative stress, altered proteostasis and autophagy networks as a result of triplication of chromosome 21(chr 21). The chr21 gene products are considered a principal neuropathogenic moiety in DS. Several genes involved respectively in the formation of senile plaques and neurofibrillary tangles (NFT), two main pathological hallmarks of AD, are mapped on chr21. Further, in subjects with DS the activation of mTOR signaling contributes to Aβ generation and the formation of NFT. This ...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research