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Lysosomal NEU1 deficiency affects amyloid precursor protein levels and amyloid-β secretion via deregulated lysosomal exocytosis. | LitMetric

AI Article Synopsis

  • - Alzheimer's disease (AD) involves harmful protein buildup in the brain, and despite extensive research, there are currently no effective treatments available.
  • - A study reveals that a deficiency in the enzyme NEU1 in mice triggers an AD-like process, causing the accumulation of a protein linked to amyloid formation and excessive release of toxic Aβ peptides.
  • - Introducing NEU1 into an established mouse model of AD significantly reduces toxic β-amyloid plaques, suggesting NEU1 could be a promising target for future AD therapies.

Article Abstract

Alzheimer's disease (AD) belongs to a category of adult neurodegenerative conditions, which are associated with intracellular and extracellular accumulation of neurotoxic protein aggregates. Understanding how these aggregates are formed, secreted and propagated by neurons has been the subject of intensive research, but so far no preventive or curative therapy for AD is available, and clinical trials have been largely unsuccessful. Here we show that deficiency of the lysosomal sialidase NEU1 leads to the spontaneous occurrence of an AD-like amyloidogenic process in mice. This involves two consecutive events linked to NEU1 loss-of-function--accumulation and amyloidogenic processing of an oversialylated amyloid precursor protein in lysosomes, and extracellular release of Aβ peptides by excessive lysosomal exocytosis. Furthermore, cerebral injection of NEU1 in an established AD mouse model substantially reduces β-amyloid plaques. Our findings identify an additional pathway for the secretion of Aβ and define NEU1 as a potential therapeutic molecule for AD.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015463PMC
http://dx.doi.org/10.1038/ncomms3734DOI Listing

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