Title:Cross-Interplay between Osmolytes and mTOR in Alzheimer's Disease Pathogenesis
Volume: 26
Issue: 37
Author(s): Zeba Mueed, Devanshu Mehta, Pankaj K. Rai, Mohammad A. Kamal and Nitesh K. Poddar*
Affiliation:
- Department of Biosciences, Manipal University Jaipur, Rajasthan,India
Keywords:
Hyperosmotic stress, osmolytes, mTOR, Aβ, tau, autophagy.
Abstract: Alzheimer’s disease, categorized by the piling of amyloid-β (Aβ), hyperphosphorylated tau, PHFs,
NFTs and mTOR hyperactivity, is a neurodegenerative disorder, affecting people across the globe. Osmolytes are
known for osmoprotectants and play a pivotal role in protein folding, function and protein stability, thus, preventing
proteins aggregation, and counteracting effects of denaturing solutes on proteins. Osmolytes (viz., sorbitol,
inositol, and betaine) perform a pivotal function of maintaining homeostasis during hyperosmotic stress. The
selective advantage of utilising osmolytes over inorganic ions by cells is in maintaining cell volume without compromising
cell function, which is important for organs such as the brain. Osmolytes have been documented not
only as neuroprotectors but they also seem to act as neurodegenerators. Betaine, sucrose and trehalose supplementation
has been seen to induce autophagy thereby inhibiting the accumulation of Aβ. In contrast, sucrose has
also been associated with mTOR hyperactivity, a hallmark of AD pathology. The neuroprotective action of
taurine is revealed when taurine supplementation is seen to inhibit neural damage, apoptosis and oxidative damage.
Inositol stereoisomers (viz., scyllo-inositol and myo-inositol) have also been seen to inhibit Aβ production
and plaque formation in the brain, inhibiting AD pathogenesis. However, TMAO affects the aging process adversely
by deregulating the mTOR signalling pathway and then kindling cognitive dysfunction via degradation of
chemical synapses and synaptic plasticity. Thus, it can be concluded that osmolytes may act as a probable therapeutic
approach for neurodevelopmental disorders. Here, we have reviewed and focussed upon the impact of
osmolytes on mTOR signalling pathway and thereby its role in AD pathogenesis.
