Affiliations: Alzheimer’s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
Correspondence:
[*]
Correspondence to: Domenico Praticò, MD, FCPP, Alzheimer’s Center at Temple, 3500 North Broad Street, MERB, suite 1160, Philadelphia, PA 19140, USA. Tel.: +1 215 707 9380; Fax: +1 215 707 2746; E-mail: [email protected].
Note: [1] Current address: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
Abstract: Background:The vacuolar protein sorting 35 (VPS35) is the main component of the retromer recognition core complex system which regulates intracellular cargo protein sorting and trafficking. Downregulation of VPS35 has been linked to the pathogenesis of neurodegenerative disorders such Alzheimer’s and Parkinson’s diseases via endosome dysregulation. Objective:Here we show that the genetic manipulation of VPS35 affects intracellular degradation pathways. Methods:A neuronal cell line expressing human APP Swedish mutant was used. VPS35 silencing was performed treating cells with VPS35 siRNA or Ctr siRNA for 72 h. Results:Downregulation of VPS35 was associated with alteration of autophagy flux and intracellular accumulation of acidic and ubiquitinated aggregates suggesting that dysfunction of the retromer recognition core leads to a significant alteration in both pathways. Conclusion:Taken together, our data demonstrate that besides cargo sorting and trafficking, VPS35 by supporting the integral function of the retromer complex system plays an important role also as a critical regulator of intracellular degradation pathways.
