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UBB+1-induced activation of autophagy reduces cytotoxicity of amyloid-β in yeast

ABSTRACT: UBB+1 is a mutated version of ubiquitin B caused by a transcriptional frameshift. The accumulation of UBB+1, has been linked to ubiquitin-proteasome system (UPS) dysfunction and neurodegeneration. Alzheimer’s disease (AD) is the most common form of neurodegeneration and accumulation of amyloid β (Aβ) in the brain is a prominent neuropathological feature of AD. In our previous study, we found that low expression of UBB+1 could protect cells against several stresses during chronological aging. Here, we applied the genome-wide expression analyses and found that low UBB+1 expression activated the autophagy pathway. Low UBB+1 expression was shown to upregulate vacuolar activity and promote transport of the ATG8p (autophagic marker) to the vacuole. To further study the effects, we expressed low level of UBB+1 in our humanized yeast Aβ models with the expression of either Aβ42 or Aβ40. Interestingly, the co-expression of UBB+1 with Aβ42 or Aβ40 showed a reduction of intracellular Aβ levels and increased chronological life span. In the autophagy deficient mutant background (atg1∆), the intracellular Aβ levels were not affected by UBB+1 expression. Our findings suggest a mechanism of UBB+1 action in reducing intracellular levels of Aβ.

ORGANISM(S): Saccharomyces cerevisiae Schizosaccharomyces pombe

PROVIDER: GSE129688 | GEO | 2021/03/12

REPOSITORIES: GEO

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