Dynein Dysfunction Reproduces Age-Dependent Retromer Deficiency: Concomitant Disruption of Retrograde Trafficking Is Required for Alteration in β-Amyloid Precursor Protein Metabolism.

We report that aging itself affects retromer trafficking in cynomolgus monkey brains. In addition, dynein dysfunction reproduces this type of age-dependent retromer deficiency (ie, the endosomal accumulation of retromer-related proteins and Aβ precursor protein. Moreover, we found that knockdown of Rab7, Rab9, or Rab11 did not alter endogenous Aβ precursor protein metabolism, such as that observed in aged monkey brains and in dynein-depleted cells. These findings suggest that dynein dysfunction can cause retromer deficiency and that concomitant disruption of retrograde trafficking may be the key factor underlying age-dependent Aβ pathology.
PMID: 27179390 [PubMed - as supplied by publisher]

Source: The American Journal of Pathology - May 10, 2016 Category: Pathology Authors: Kimura N, Samura E, Suzuki K, Okabayashi S, Shimozawa N, Yasutomi Y Tags: Am J Pathol Source Type: research