Chapter 10: Autophagy: Role in Alzheimer's Disease Pathophysiology and Therapeutic Avenues Check Access

Neurodegenerative diseases such as Alzheimer's disease (AD) are often regarded as proteinopathic disorders owing to the aberrant accumulation of misfolded protein aggregates which acquire neurotoxic properties. The impaired clearance and accumulation of oligomerized, misfolded protein aggregates, may be mainly attributed to a disruption in autophagy-mediated substrate degradation, which is now considered to be a major hallmark of AD pathology. As a result of hindrance in different steps of the autophagy pathway, autophagic vacuoles (AVs) accumulate in vast numbers in the dystrophic neurites of the AD brain. In this chapter, we discuss recent understanding of autophagy dysfunction in the pathophysiology of AD, in the context of neurons as well as glial cells such as microglia and astrocytes. We also highlight the intricate and dual relationship between Aβ metabolism and autophagy and how autophagy is involved in a vicious cross-talk with other cellular pathways such as apoptosis and neuroinflammation. Finally, we put together several therapeutic approaches which are recently being considered to target different steps in the autophagy pathway in order to promote the clearance of neurotoxic misfolded protein aggregates. Therapies aimed at improving clearance mechanisms would be very useful in curtailing the onset and progression of AD.