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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Impairment of mitochondria dynamics by human A53T alpha-synuclein and rescue by NAP (davunetide) in a cell model for Parkinson's disease

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Melo, T. Q. ; van Zomeren, K. C. ; Ferrari, M. F. R. ; Boddeke, H. W. G. M. ; Copray, J. C. V. M.
Total Authors: 5
Document type: Journal article
Source: Experimental Brain Research; v. 235, n. 3, p. 731-742, MAR 2017.
Web of Science Citations: 9

The formation of oligomers and aggregates of overexpressed or mutant alpha-synuclein play a role in the degeneration of dopaminergic neurons in Parkinson's disease by causing dysfunction of mitochondria, reflected in their disturbed mobility and production of ROS. The mode of action and mechanisms underlying this mitochondrial impairment is still unclear. We have induced stable expression of wild-type, A30P or A53T alpha-synuclein in neuronally differentiated SH-SY5Y neuroblastoma cells and studied anterograde and retrograde mitochondrial trafficking in this cell model for Parkinson's disease. In contrast to wild-type and A30P, A53T alpha-synuclein significantly inhibited mitochondrial trafficking, at first retrogradely and in a later stage anterogradely. Accordingly, A53T alpha-synuclein also caused the highest increase in ROS production in the dysmobilized mitochondria in comparison to wild-type or A30P alpha-synuclein. Treatment with NAP, the eight amino acid peptide identified as the active component of activity-dependent neuroprotective protein (ADNP), completely annihilated the adverse effects of A53T on mitochondrial dynamics. Our results reveal that A53T alpha-synuclein (oligomers or aggregates) leads to the inhibition of mitochondrial trafficking, which can be rescued by NAP, suggesting the involvement of microtubule disruption in the pathophysiology of Parkinson's disease. (AU)

FAPESP's process: 12/15495-2 - Mitochondria trafficking and autophagy in human dopaminergic neurons derived from embryonic and induced-pluripotent stem cells
Grantee:Merari de Fátima Ramires Ferrari
Support Opportunities: Regular Research Grants
FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC