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Peripherin Pathology

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Cytoskeleton of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 3))

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Abstract

Peripherin, a 58-kDa, type III intermediate filament (IF) protein expressed in the peripheral nervous system (PNS) and in defined subsets of neurons in the central nervous system (CNS), is thought to play an integral role in the development of the highly plastic neuronal cytoskeleton and to provide mechanical support to terminally differentiated neurons. Peripherin expression is a dynamically regulated process that involves mediation by a number of cis- and trans-acting factors throughout the gene region. Peripherin expression is characterized by a stoichiometric ratio of functionally distinct isoforms that arise as a result of alternative splicing and translation. Pathologically, peripherin has been implicated in several human diseases but is best known for its descriptions in the literature of the devastating motor neuron disease, amyotrophic lateral sclerosis (ALS). Here, peripherin is a component of the major pathologic hallmarks of both familial and sporadic ALS – intracellular aggregates – and is found upregulated and abnormally spliced in areas of disease. Moreover, peripherin mutations have been associated with sporadic ALS cases, and transgenic overexpression of peripherin in mice recapitulates some of the clinical and pathologic aspects of ALS. Peripherin pathology represents a point-of-convergence for both the familial and sporadic forms of ALS; however, despite our increasing knowledge about peripherin biology, little is known about the nature of its involvement in disease pathogenesis. This chapter is aimed at providing the first intensive review of peripherin biology and its involvement in disease.

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Authors and Affiliations

  1. Center for Neuroregeneration Research, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA

    Jesse R. McLean

  2. Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada, M5S 3H2

    Janice Robertson

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    Ralph A. Nixon

  2. Psychiatric Research, Nathan S. Kline Institute for, 140 Old Orangeburg Road, Orangeburg, 10962, New York, USA

    Aidong Yuan

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McLean, J.R., Robertson, J. (2011). Peripherin Pathology. In: Nixon, R., Yuan, A. (eds) Cytoskeleton of the Nervous System. Advances in Neurobiology, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6787-9_9

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