Abstract
The hyperphosphorylation of tau protein and the overexpression of mTOR are considered to be the driving force behind Aβ plaques and Neurofibrillay Tangles (NFT's), hallmarks of Alzheimer's disease (AD). It is now evident that miscellaneous diseases such as Diabetes, Autoimmune diseases, Cancer, etc. are correlated with AD. Therefore, we reviewed the literature on the causes of AD and investigated the association of tau and mTOR with other diseases. We have discussed the role of insulin deficiency in diabetes, activated microglial cells, and dysfunction of blood-brain barrier (BBB) in Autoimmune diseases, Presenilin 1 in skin cancer, increased reactive species in mitochondrial dysfunction and deregulated Cyclins/CDKs in promoting AD pathogenesis. We have also discussed the possible therapeutics for AD such as GSK3 inactivation therapy, Rechaperoning therapy, Immunotherapy, Hormonal therapy, Metal chelators, Cell cycle therapy, γ-secretase modulators, and Cholinesterase and BACE 1-inhibitors which are thought to serve a major role in combating pathological changes coupled with AD. Recent research about the relationship between mTOR and aging and hepatic Aβ degradation offers possible targets to effectively target AD. Future prospects of AD aims at developing novel drugs and modulators that can potentially improve cell to cell signaling, prevent Aβ plaques formation, promote better release of neurotransmitters and prevent hyperphosphorylation of tau.
Highlights
The most prevalent type of dementia, which is known to be occuring worldwide is Alzheimer’s disease (AD), affecting more than 40 million people worldwide (Selkoe and Hardy, 2016) and which is expected to get tripled by 2050 (Galvan and Hart, 2016)
This review summarizes the role of Aβ and tau and their close interplay with mTOR and autophagy in AD progression as well as their role as a trigger for clinical diseases in promoting AD such as autoimmunity, mitochondrial dysfunction etc. (Lim et al, 2007; Fernandez et al, 2009) along with different therapeutic approaches aimed at targeting AD from progressing
Another important point to note is that PI3-K/Akt acts on mTOR to promote autophagy and in turn enhances Aβ clearance and reduces the hyperphosphorylation of tau (Chong et al, 2012)
Summary
The most prevalent type of dementia, which is known to be occuring worldwide is Alzheimer’s disease (AD), affecting more than 40 million people worldwide (Selkoe and Hardy, 2016) and which is expected to get tripled by 2050 (Galvan and Hart, 2016). Some important upstream components which activate mTOR are phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), glycogen synthase kinase 3 (GSK3), AMP-activated protein kinase (AMPK), and insulin/insulin-like growth factor 1 (IGF-1) (Figure 1). On account of this fact, current research study is mainly focusing on to create inhibitors of mTOR which will eventually help in limiting the progression of AD. Activation of mTOR than leads to the pathological changes coupled to AD Another important point to note is that PI3-K/Akt acts on mTOR to promote autophagy and in turn enhances Aβ clearance and reduces the hyperphosphorylation of tau (Chong et al, 2012). Researchers believe that hypoglycemic drugs may be valuable for treating AD (Baker et al, 2011) (Figure 1)
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