The role of neurofilament aggregation in neurodegeneration: lessons from rare inherited neurological disorders

• Published in: Molecular neurodegeneration Vol. 14; no. 1; pp. 19 - 10
• Main Authors: Didonna, Alessandro, Opal, Puneet
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.05.2019; BioMed Central; BMC
• Subjects: Alzheimer's disease; Amyotrophic lateral sclerosis; Ataxia; Atrophy; Axonal plasticity; Care and treatment; Charcot-Marie-tooth (CMT) disease; Conduction; Cytoskeleton; Dementia; Diabetic neuropathy; Filaments; Gene mutation; Genetic aspects; Giant axonal neuropathy (GAN); Intermediate filament proteins; Intermediate filaments; Mutation; Nervous system; Nervous system diseases; Neurodegeneration; Neurodegenerative diseases; Neurofilaments; Neurological diseases; Neurological disorders; Neurons; Neurotransmitter receptors; Parkinson's disease; Phosphatase; Phosphorylation; Polymers; Protein aggregation; Protein degradation; Proteins; Proteolysis; Review; Synaptic plasticity; Synaptic vesicles; Giant axonal neuropathy (GAN); Neurofilaments; Charcot-Marie-tooth (CMT) disease; Protein aggregation; Protein degradation; Neurodegeneration
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-019-0318-4

Many neurodegenerative disorders, including Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis, are well known to involve the accumulation of disease-specific proteins. Less well known are the accumulations of another set of proteins, neuronal intermediate filaments (NFs), which have been observed in these diseases for decades. NFs belong to the family of cytoskeletal intermediate filament proteins (IFs) that give cells their shape; they determine axonal caliber, which controls signal conduction; and they regulate the transport of synaptic vesicles and modulate synaptic plasticity by binding to neurotransmitter receptors. In the last two decades, a number of rare disorders caused by mutations in genes that encode NFs or regulate their metabolism have been discovered. These less prevalent disorders are providing novel insights into the role of NF aggregation in the more common neurological disorders.