Protein may advance Parkinson's by preventing neurons from clearing debris

September 20, 2010

A protein linked to Parkinson's disease may cause neurodegeneration by inhibiting autophagy -- the process in which cells digest some of their contents -- according to a study in the September 20 issue of the Journal of Cell Biology.

Autophagy serves to clear a variety of toxic waste from , including misfolded proteins and defective mitochondria. These two types of cellular trash accumulate in from Parkinson's patients, suggesting that autophagy could be impaired in these cells. A commonly amassed protein in Parkinson's disease is alpha-synuclein, whose gene is often mutated or overexpressed in familial forms of the illness. David Rubinsztein and researchers from the University of Cambridge in England found that excess alpha-synuclein inhibits autophagy by blocking formation of the autophagosome—the double-membraned vesicle that engulfs cytoplasmic garbage and delivers it to lysosomes for destruction.

Previous research revealed that alpha-synuclein inhibits Rab1a, a small GTPase that controls secretory transport from the to the Golgi. Rubinsztein and colleagues now provide new insight into the role Rab1a plays in autophagy, and why blocking it has such dire consequences. The team found that lack of Rab1a impaired autophagosome formation, whereas an abundance of the GTPase reversed the inhibitory effects of alpha-synuclein on autophagy. Rab1a and alpha-synuclein act specifically at an early stage of autophagosome formation: an abundance of alpha-synuclein or lack of Rab1a disrupted an early acting part of the autophagy machinery called Atg9 and blocked the formation of autophagosome precursors known as omegasomes.

Alpha-synuclein's blockade of autophagy could enhance the gradual accumulation of toxic proteins and dysfunctional mitochondria, sensitizing neurons to .

Explore further: Einstein researchers discover important clue to the cause of Parkinson's disease

More information: Winslow, A.R., et al. 2010. J. Cell Biol. doi:10.1083/jcb.201003122

Related Stories

Cell recycling protects tumor cells from anti-cancer therapy

March 6, 2008

Cells have their own recycling system: Discarded cellular components, from individual proteins through to whole cellular organs, are degraded and the building blocks re-used in a different place. The scientific term for this ...

Toxicity mechanism identified for Parkinson's disease

January 2, 2009

Neurologists have observed for decades that Lewy bodies, clumps of aggregated proteins inside cells, appear in the brains of patients with Parkinson's disease and other neurodegenerative diseases.

How the pathology of Parkinson's disease spreads

July 27, 2009

( -- Accumulation of the synaptic protein alpha-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson's and other related neurodegenerative diseases. ...

Yeast holds clues to Parkinson's disease

September 9, 2010

Yeast could be a powerful ally in the discovery of new therapeutic drugs to treat Parkinson's disease says a scientist presenting his work at the Society for General Microbiology's autumn meeting in Nottingham today.

Recommended for you

Study suggests fish can experience 'emotional fever'

November 25, 2015

(—A small team of researchers from the U.K. and Spain has found via lab study that at least one type of fish is capable of experiencing 'emotional fever,' which suggests it may qualify as a sentient being. In their ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.