Mechanisms of distal axonal degeneration in peripheral neuropathies.
Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wld(S)) and Sarm knockout animal models. These studies have shown axonal degeneration to occur through a programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration.
['Cashman|Christopher R|CR|', 'Höke|Ahmet|A|']
D001370:Axonal Transport D016123:Campylobacter jejuni D003929:Diabetic Neuropathies D004721:Endoplasmic Reticulum D006678:HIV D016174:Hepacivirus D006801:Humans D007249:Inflammation D007473:Ion Channels D008928:Mitochondria D015388:Organelles D010523:Peripheral Nervous System Diseases D017382:Reactive Oxygen Species D015398:Signal Transduction
Peripheral neuropathy Diabetes Campylobacter jejuni Wld(S) Chemotherapy induced peripheral neuropathy Guillain–Barré syndrome HIV neuropathy Mechanisms of neuropathy Mitochondrial aging Post-infectious neuropathy