Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases
Abstract
In autophagy long-lived proteins, protein aggregates or damaged organelles are engulfed by vesicles called autophagosomes prior to lysosomal degradation. Autophagy dysfunction is a hallmark of several neurodegenerative diseases in which misfolded proteins or dysfunctional mitochondria accumulate. Excessive autophagy can also exacerbate brain injury under certain conditions. In this review, we provide specific examples to illustrate the critical role played by autophagy in pathological conditions affecting the brain and discuss potential therapeutic implications. We show how a singular type of autophagy-dependent cell death termed autosis has attracted attention as a promising target for improving outcomes in perinatal asphyxia and hypoxic-ischaemic injury to the immature brain. We provide evidence that autophagy inhibition may be protective against radiotherapy-induced damage to the young brain. We describe a specialized form of macroautophagy of therapeutic relevance for motoneuron and neuromuscular diseases, known as chaperone-assisted selective autophagy, in which heat shock protein B8 is used to deliver aberrant proteins to autophagosomes. We summarize studies pinpointing mitophagy mediated by the serine/threonine kinase PI...Continue Reading
References
Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death
The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia
Abnormal small heat shock protein interactions involving neuropathy-associated HSP22 (HSPB8) mutants
Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain.
Citations
Related Concepts
Related Feeds
Parkinson's Disease & Autophagy
Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.
Autophagosome
An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.
Brain Injury & Trauma
brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.
Autophagy & Disease
Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.
Autophagosome
An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.
Parkinson's Disease & Autophagy (MDS)
Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.
Autophagy & Model Organisms
Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms