Abstract
Neurodegenerative diseases (NDDs) such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease (HD), amyotrophic lateral sclerosis, and prion diseases are all characterized by the accumulation of protein aggregates (amyloids) into inclusions and/or plaques. The ubiquitous presence of amyloids in NDDs suggests the involvement of disturbed protein homeostasis (proteostasis) in the underlying pathomechanisms. This review summarizes specific mechanisms that maintain proteostasis, including molecular chaperons, the ubiquitin-proteasome system (UPS), endoplasmic reticulum associated degradation (ERAD), and different autophagic pathways (chaperon mediated-, micro-, and macro-autophagy). The role of heat shock proteins (Hsps) in cellular quality control and degradation of pathogenic proteins is reviewed. Finally, putative therapeutic strategies for efficient removal of cytotoxic proteins from neurons and design of new therapeutic targets against the progression of NDDs are discussed.
Highlights
Several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and prion disease are, among others, characterized by the presence of specific proteinaceous inclusions in or around the affected neurons
Transgenic overexpression of HspA1A reduces Aβ plaque formation, neuronal loss, and cognitive deficits in a mouse model of AD [151]. These results indicate that overexpression of heat shock proteins (Hsps) ameliorates certain symptoms of neurodegenerative diseases
Several pathways are responsible for balancing brain proteostasis
Summary
Several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and prion disease are, among others, characterized by the presence of specific proteinaceous inclusions in or around the affected neurons. These inclusions are composed of misfolded, aggregated, and often toxic forms of specific proteins (Table 1). Misfolded polypeptides are cleared through ER-associated protein degradation (ERAD) which targets misfolded proteins within the ER for ubiquitination and subsequent degradation by the proteasome (ubiquitin-proteasome system, UPS), and through different autophagy pathways (chaperon-mediated-, macro-, or micro-autophagy). Considering the role of Hsps in efficient clearance of irreversible misfolded polypeptides, we focus on particular synthetic and natural Hsp-inducers or co-inducers with potential therapeutic value
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
