Alsin and the molecular pathways of amyotrophic lateral sclerosis

Jayanth Chandran, Jinhui Ding, Huaibin Cai

    Research output: Contribution to journalReview articlepeer-review

    Abstract

    Autosomal recessive mutations in the ALS2 gene lead to a clinical spectrum of motor dysfunction including juvenile onset amyotrophic lateral sclerosis (ALS2), primary lateral sclerosis, and hereditary spastic paraplegia. The 184-kDa alsin protein, encoded by the full-length ALS2 gene, contains three different guanine-nucleotide-exchange factor-like domains, which may play a role in the etiology of the disease. Multiple in vitro biochemical and cell biology assays suggest that alsin dysfunction affects endosome trafficking through a Rab5 small GTPase family-mediated mechanism. Four ALS2-deficient mouse models have been generated by different groups and used to study the behavioral and pathological impact of alsin deficiency. These mouse models largely fail to recapitulate hallmarks of motor neuron disease, but the subtle deficits that are observed in behavior and pathology have aided in our understanding of the relationship between alsin and motor dysfunction. In this review, we summarize recent clinical and molecular reports regarding alsin and attempt to place these results within the larger context of motor neuron disease.

    Original languageEnglish (US)
    Pages (from-to)224-231
    Number of pages8
    JournalMolecular Neurobiology
    Volume36
    Issue number3
    DOIs
    StatePublished - Dec 2007

    Keywords

    • ALS2
    • Alsin
    • Amyotrophic lateral sclerosis (ALS)
    • Guanine-nucleotide-exchange factor
    • Hereditary spastic paraplegia
    • Mouse model
    • Primary lateral sclerosis
    • Rab5

    ASJC Scopus subject areas

    • Neurology
    • Cellular and Molecular Neuroscience

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