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Peripherin‐mediated death of motor neurons rescued by overexpression of neurofilament NF‐H proteins
Author(s) -
Beaulieu JeanMartin,
Julien JeanPierre
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01653.x
Subject(s) - peripherin , neurofilament , amyotrophic lateral sclerosis , intermediate filament , inclusion bodies , motor neuron , microbiology and biotechnology , biology , genetically modified mouse , intermediate filament protein , transgene , neuroscience , spinal cord , pathology , immunology , biochemistry , gene , cytoskeleton , immunohistochemistry , medicine , cell , disease , escherichia coli
Abstract In previous studies, we showed that overexpression of peripherin, a neuronal intermediate filament (IF) protein, in mice deficient for neurofilament light (NF‐L) subunits induced a progressive adult‐onset degeneration of spinal motor neurons characterized by the presence of IF inclusion bodies reminiscent of axonal spheroids found in amyotrophic lateral sclerosis (ALS). In contrast, the overexpression of human neurofilament heavy (NF‐H) proteins provoked the formation of massive perikaryal IF protein accumulations with no loss of motor neurons. To further investigate the toxic properties of IF protein inclusions, we generated NF‐L null mice thatco‐express both peripherin and NF‐H transgenes. The axonal count in L5 ventral roots from 6 and 8‐month‐old transgenic mice showed that NF‐H overexpression rescued the peripherin‐mediated degeneration of motor neurons. Our analysis suggests that the protective effect of extra NF‐H proteins is related to the sequestration of peripherin into the perikaryon of motor neurons, thereby abolishing the development of axonal IF inclusions that might block transport. These findings illustrate the importance of IF protein stoichiometry in formation, localization and toxicity of neuronal inclusion bodies.