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Neurodegener Dis. 2011;8(4):262-74. doi: 10.1159/000321547. Epub 2010 Dec 3.

TDP-43-based animal models of neurodegeneration: new insights into ALS pathology and pathophysiology.

Author information

1
Neuromuscular Division, Department of Neurology, Washington University, Saint Louis, MO 63110, USA.

Abstract

The clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) suggests these diseases share common underlying mechanisms, a suggestion underscored by the discovery that TDP-43 inclusions are a key pathologic feature in both ALS and FTLD. This finding, combined with the identification of TDP-43 mutations in ALS, directly implicates this DNA/RNA binding protein in disease pathogenesis in ALS and FTLD. However, many key questions remain, including what is the normal function of TDP-43, and whether disease-associated mutations produce toxicity in the nucleus, cytoplasm or both. Furthermore, although pathologic TDP-43 inclusions are clearly associated with many forms of neurodegeneration, whether TDP-43 aggregation is a key step in the pathogenesis in ALS, FTLD and other disorders remains to be proven. This review will compare the features of numerous recently developed animal models of TDP-43-related neurodegeneration, and discuss how they contribute to our understanding of the pathogenesis of human ALS and FTLD.

PMID:
21124004
PMCID:
PMC3214943
DOI:
10.1159/000321547
[Indexed for MEDLINE]
Free PMC Article

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