Neurofilaments and neurological disease

Departments of Neuroscience and Neurology, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
BioEssays (Impact Factor: 4.84). 04/2003; 25(4):346-55. DOI: 10.1002/bies.10251
Source: PubMed

ABSTRACT Neurofilaments are one of the major components of the neuronal cytoskeleton and are responsible for maintaining the calibre of axons. They are modified by post-translational changes that are regulated in complex fashions including by the interaction with neighbouring glial cells. Neurofilament accumulations are seen in several neurological diseases and neurofilament mutations have now been associated with Charcot-Marie-Tooth disease, Parkinson's disease and amyotrophic lateral sclerosis. In this review, we discuss the structure, normal function and molecular pathology of neurofilaments.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Compelling evidence now points to the critical role of the cytoskeleton in neurodegeneration. In the present study, using an immunohistochemical approach, we have shown that cortical stab injury (CSI) in adult Wistar rats significantly affects temporal pattern of expression of neurofilament proteins (NFs), a major cytoskeleton components of neurons, and microtubule-associated proteins (MAP2). At 3 days post-injury (dpi) most of the NFs immunoreactivity was found in pyknotic neurons and in fragmentized axonal processes in the perilesioned cortex. These cytoskeletal alterations became more pronounced by 10dpi. At the subcellular level CSI also showed significant impact on NFs and MAP-2 expression. Thus, at 3dpi most of the dendrites disappeared, while large neuronal somata appeared like open circles pointing to membrane disintegration. Conversely, at 10dpi neuronal perikarya and a few new apical dendrites were strongly labeled. Since aberrant NF phosphorylation is a pathological hallmark of many human neurodegenerative disorders, as well as is found after stressor stimuli, the present results shed light into the expression of neurofilaments after the stab brain injury. Copyright © 2014 Elsevier GmbH. All rights reserved.
    Acta Histochemica 01/2015; 117(2). DOI:10.1016/j.acthis.2014.12.004 · 1.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS [MIM 270550]) is an early-onset neurodegenerative disorder caused by mutations in the SACS gene. Over 170 SACS mutations have been reported worldwide and are thought to cause loss of function of sacsin, a poorly characterized and massive 520 kDa protein. To establish an animal model and to examine the pathophysiological basis of ARSACS, we generated Sacs knockout (Sacs(-/-)) mice. Null animals displayed an abnormal gait with progressive motor, cerebellar, and peripheral nerve dysfunctions highly reminiscent of ARSACS. These clinical features were accompanied by an early onset, progressive loss of cerebellar Purkinje cells followed by spinal motor neuron loss and peripheral neuropathy. Importantly, loss of sacsin function resulted in abnormal accumulation of non-phosphorylated neurofilament (NF) bundles in the somatodendritic regions of vulnerable neuronal populations, a phenotype also observed in an ARSACS brain. Moreover, motor neurons cultured from Sacs(-/-) embryos exhibited a similar NF rearrangement with significant reduction in mitochondrial motility and elongated mitochondria. The data point to alterations in the NF cytoskeleton and defects in mitochondria dynamics as the underlying pathophysiological basis of ARSACS.
    Human Molecular Genetics 09/2014; 24(3). DOI:10.1093/hmg/ddu491 · 6.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nowadays, depression is a serious psychological disorder that causes extreme economic loss and social problems. Previously, we discovered that the water extract of Gastrodia elata Blume (WGE) improved the depressive-like behavior by influencing neurotransmitters in rats subjected to forced swimming test (FST). To elucidate possible mechanisms, in the present study, we performed a proteomics and bioinformatics analysis to identify the related pathways. Western blot-validated results indicated that the core protein network modulated by WGE administration, were closely associated with down-regulation of Slit-Robo pathway which modulates neuronal cytoskeletal remodeling processes. Although Slit-Robo signaling has been well investigated in neuronal development, its relationship with depression is not fully understood. We provide a potential hint on the mechanism responsible for the antidepressive-like activity of WGE. In conclusion, we suggest that Slit-Robo pathway and neuronal cytoskeleton remodeling are possibly to be one of the pathways associated with the antidepressive-like effects of WGE.
    Journal of Agricultural and Food Chemistry 09/2014; 62(43). DOI:10.1021/jf503132c · 3.11 Impact Factor