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Curr Pharm Des. 2020;25(43):4560-4569. doi: 10.2174/1381612825666191210154535.

Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders.

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Department of Neurology, National Taiwan University Hospital, Hsinchu Branch, Hsinchu, Taiwan, China.
Department of Geriatrics, Northern Beaches Hospital, Frenchs Forest New South Wales, Australia.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vacover, BC V6T1Z4, Canada.
Institute of Biomedical Engineering, National Chiao Tung University, Hsinchu, Taiwan, China.


Neurofilaments: light, medium, and heavy (abbreviated as NF-L, NF-M, and NF-H, respectively), which belong to Type IV intermediate filament family (IF), are neuron-specific cytoskeletal components. Neurofilaments are axonal structural components and integral components of synapses, which are important for neuronal electric signal transmissions along the axons and post-translational modification. Abnormal assembly of neurofilaments is found in several human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy (SMA), and hereditary sensory-motor neuropathy (HSMN). In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson's disease (PD), Aβ and tau in Alzheimer's disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS). When axon damage occurs in central nervous disorders, neurofilament proteins are released and delivered into cerebrospinal fluid (CSF), which are then circulated into blood. New quantitative analyses and assay techniques are well-developed for the detection of neurofilament proteins, particularly NF-L and the phosphorylated NF-H (pNF-H) in CSF and serum. This review discusses the potential of using peripheral blood NF quantities and evaluating the severity of damage in the nervous system. Intermediate filaments could be promising biomarkers for evaluating disease progression in different nervous system disorders.


Neurofilament; biomarker; cerebrospinal fluid; intermediate filament; mass spectrometry; nervous system disorders.

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