What causes neuronal cell death in Parkinson disease?

Michael J. Fox (photo by Alan Light)

Michael J. Fox (photo by Alan Light)

The leucine-rich repeat kinase 2 (LRRK2) gene codes for a protein kinase that has the ability to function in a dominant way to cause neurodegeneration. Mutations in the human LRRK2 gene can cause Parkinson disease.

The LRRK2 protein and it role in brain function has been studied for the past five years. It has a complex domain structure and has been reported to interact with several other proteins including parkin.  Some disease-causing variants of LRRK2 have an increased amount of protein kinase activity so there is interest in finding inhibitors of LRRK2.

Ted Dawson’s team at the Johns Hopkins Institute for Cell Engineering has done experiments with laboratory mice engineered to carry Parkinson-causing LRRK2 and experience neuronal cell death. They found some drugs that inhibit  LRRK2 and that gave protection against neuronal cell death (Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson’s disease, published in September 2010).

On December 15, 2010 a research report was published showing that LRRK2 can influence the development of synapses between neurons and muscle cells in Drosophila (“LRRK2 Kinase Regulates Synaptic Morphology through Distinct Substrates at the Presynaptic and Postsynaptic Compartments of the Drosophila Neuromuscular Junction“). Several labs are using the fruit fly Drosophila as a convenient experimental system for study of the function of LRRK2 in neurons (see “A Drosophila model for LRRK2-linked parkinsonism“). Might LRRK2 play a normal physiological role in the formation of synapses? Disease-causing variants of LRRK2 might have abnormal synaptic connections that lead to neurodegeneration.

Domain structure of the LRRK2 protein.

Domain structure of the LRRK2 protein.

Related Reading:

2017. The LRRK2–macroautophagy axis and its relevance to Parkinson’s disease.


Biochemical and molecular features of LRRK2 and its pathophysiological roles in Parkinson’s disease (PDF file)

Newsflash: a possible mechanism for Parkinson’s disease” posted on July 31, 2010 by Sam W

Sergey Brin describes his family as having a disease causing LRRK2 gene variant.

The Michael J. Fox Foundation for Parkinson’s Research is funding research targeting LRRK2.
Image creditsPhoto of Michael J. Fox by Alan Light.

Related blog post. Calcium channels and neurodegeneration


About johnwschmidt

Exploring medical physiology.
This entry was posted in Diseases, Parkinson disease and tagged , , , , , . Bookmark the permalink.

One Response to What causes neuronal cell death in Parkinson disease?

  1. Pingback: Gap junctions in the brain | medicalneurophys

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