Role of Parkin, PINK 1 in protection of dopamine neurons
 

Study reveals the role of Parkin and PINK1 in Parkinson's disease - CUSABIO Life science | cusabio.com


Proteasome - Wikipedia

Press Release and Research Paper
 

The press release has some more information:

Targeting Parkinson’s-Linked Protein Could Neutralize 2 of the Disease’s Causes - 2/1/217

The research paper itself is also available:

http://www.cell.com/cell-reports/abs...247(16)31812-5

(this is an "Open Access" article)

Simplistic Thoughts
 

After reading this, and other, research papers, here are some thoughts. These thoughts are admittedly limited and very simplistic. Feel free to jump in and correct any mis-understandings, omissions, or any other errors.

My understanding of the "normal" relationship between the proteins PINK1, parkin, and PARIS is as follows:

PINK1 proteins phosphorylate PARIS proteins, and this then enables parkin proteins to ubiquitinate PARIS proteins, and this then enables PARIS proteins to be degraded by proteasomes. This keeps the number of PARIS proteins in check, thus ensuring that dopamine neurons are not killed by excess amounts of the PARIS protein.

However, in PWPs, something interferes with parkin, and this stops parkin from being able to ubiquitinate PARIS.

From reference [1], there is a strong candidate for what that "something" might be, and that is the c-Abl protein. There is already at least one promising drug (nilotinib) which targets c-Abl.

However, a new drug which targets PARIS directly could also be worthwhile. For example, some PWPs cannot tolerate nilotinib, even in small doses.

[1] Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration, Saurav Brahmachari et al., J Clin Invest. 2016;126(8):2970–2988. doi:10.1172/JCI85456.