Alzheimer's disease is characterized by neurofibrillary tangles composed of aggregates of truncated and hyperphosphorylated tau protein, but the mechanisms of their formation are understood poorly. The authors showed that in a mouse model of Alzheimer's disease, deletion of asparagine endopeptidase (AEP; a lysosomal cysteine proteinase) reduced tau hyperphosphorylation and cognitive deficits associated with Alzheimer's disease. Adeno-associated viral delivery of degradation-resistant tau had a similar effect, and suggests a role for AEP in tau-associated neurodegeneration.
References
Zhang, Z. et al. Cleavage of tau by asparagine endopeptidase mediates the neurofibrillary pathology in Alzheimer's disease. Nature Med. http://dx.doi.org/10.1038/nm.3700 (2014)
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Lewis, S. Tangled up. Nat Rev Neurosci 15, 768 (2014). https://doi.org/10.1038/nrn3866
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DOI: https://doi.org/10.1038/nrn3866