Abstract
Pathways governing protein homeostasis are involved in maintaining the structural, quantitative, and functional stability of intracellular proteins and involve the ubiquitin–proteasome system, autophagy, endoplasmic reticulum, and mTOR pathway. Due to the broad physiological implications of protein homeostasis pathways, dysregulation of proteostasis is often involved in the development of multiple pathological conditions, including Alzheimer's disease (AD). Similar to other neurodegenerative diseases that feature pathogenic accumulation of misfolded proteins, Alzheimer's disease is characterized by two pathological hallmarks, amyloid‐β (Aβ) plaques and tau aggregates. Knockout or transgenic overexpression of various proteostatic components in mice results in AD‐like phenotypes. While both Aβ plaques and tau aggregates could in turn enhance the dysfunction of these proteostatic pathways, eventually leading to apoptotic or necrotic neuronal death and pathogenesis of Alzheimer's disease. Therefore, targeting the components of proteostasis pathways may be a promising therapeutic strategy against Alzheimer's disease.
Highlights
The hyperphosphorylation state of tau facilitates the formation of intracellular tangles, which directly disrupts neuronal homeostasis and culminates in aberrant cell death (Iqbal, Liu & Gong, 2016)
MTOR cascade and endoplasmic reticulum serve as the upstream elements inside the proteostatic system, which determine the synthesis and conformation of target proteins while ubiquitin–proteasome system and autophagy act as main scavengers of misfolded or excessive proteins, regarded as the final step of proteostatic machinery
Analogous to other neurodegenerative disorders, the main cause of Alzheimer's disease is the accumulation of misfolded proteins, known as Aβ plaques and tau aggregates
Summary
The hyperphosphorylation state of tau facilitates the formation of intracellular tangles, which directly disrupts neuronal homeostasis and culminates in aberrant cell death (Iqbal, Liu & Gong, 2016). Similar as other neurodegenerative disorders, the initiation and progression of AD are correlated to the accumulation of misfolded proteins, known as Aβ plaques and tau tangles that contribute to the progressive neuronal loss and cognitive impairment (Ciechanover & Kwon, 2015; DeToma, Salamekh, Ramamoorthy, & Lim, 2012).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
