Feedforward activation of PRKN/parkin.
Rayan FakihVéronique SauvéKalle GehringPublished in: Autophagy (2022)
Parkinson disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the midbrain. The majority of early onset forms of Parkinson disease are a result of autosomal mutations in PRKN (parkin RBR E3 ubiquitin protein ligase) and PINK1 (PTEN induced kinase 1), which together regulate the clearance of damaged mitochondria from cells through selective autophagy of mitochondria (mitophagy). In a pair of recent papers, we characterized a secondary mechanism of activation of PRKN by PINK1 that is responsible for approximately a quarter of mitophagy in a cellular model. Our deepening understanding of PRKN-PINK1 signaling affords hope for the development of small molecule therapeutics for the treatment of Parkinson disease.
Keyphrases
- parkinson disease
- small molecule
- early onset
- cell death
- protein protein
- deep brain stimulation
- cell cycle arrest
- late onset
- induced apoptosis
- endoplasmic reticulum stress
- signaling pathway
- multiple sclerosis
- reactive oxygen species
- oxidative stress
- diabetic rats
- spinal cord
- high glucose
- pi k akt
- cell proliferation
- combination therapy
- amino acid
- drug induced
- protein kinase
- spinal cord injury