Abstract
Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic amyloid proteins is suspected to be one of the main causative factors in the disease pathogenesis. It is therefore important to more clearly understand how these toxic amyloid proteins accumulate as this will aide in the development of more effective preventive and therapeutic strategies. Protein homeostasis, or proteostasis, is maintained by multiple cellular pathways—including protein synthesis, quality control, and clearance—which are collectively responsible for preventing protein misfolding or aggregation. Modulating protein degradation is a very complex but attractive treatment strategy used to remove amyloid and improve cell survival. This review will focus on autophagy, an important clearance pathway of amyloid proteins, and strategies for using it as a potential therapeutic target for amyloid diseases. The physiological role of autophagy in cells, pathways for its modulation, its connection with apoptosis, cell models and caveats in developing autophagy as a treatment and as a biomarker is discussed.
Highlights
Amyloids are aggregates of proteins that become folded into a structure that allows multiple copies of that protein to accumulate, forming potentially toxic fibrous deposits in cells and tissues [1]
Molecules 2019, 24, 3372 pathological amyloids, the fibrous proteins aggregate into toxic forms that causes cell death, which leads to tissue and organ damage, culminating into clinical symptoms [3]
Recent studies have focused on a particular cellular degradation pathway known as autophagy where its dysfunction is implicated in Alzheimer’s disease (AD) and other amyloid diseases and its modulation may provide useful therapeutic pathways in treatment, which will be covered in this review
Summary
Amyloids are aggregates of proteins that become folded into a structure that allows multiple copies of that protein to accumulate, forming potentially toxic fibrous deposits in cells and tissues [1]. Molecules 2019, 24, 3372 pathological amyloids, the fibrous proteins aggregate into toxic forms that causes cell death, which leads to tissue and organ damage, culminating into clinical symptoms [3] Some cells, such as neurons, are more vulnerable to protein aggregation—which is evident when observing neurodegenerative disorders. Recent studies have focused on a particular cellular degradation pathway known as autophagy where its dysfunction is implicated in AD and other amyloid diseases and its modulation may provide useful therapeutic pathways in treatment, which will be covered in this review This pathway is responsible for degradation and recycling of misfolded or aggregated proteins and damaged organelles as well as other cellular components [10]. Other amyloid clearance pathways will be discussed in this review as well
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 call
