Mitochondrial homeostasis in Parkinson's disease - a triumvirate rule?

• Published in: Neural regeneration research Vol. 12; no. 8; pp. 1270 - 1272
• Main Authors: Ng, Chee-Hoe, Hang, Liting, Lim, Kah-Leong
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Media Pvt. Ltd 01.08.2017; Medknow Publications & Media Pvt. Ltd; National Neuroscience Institute, Singapore; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Adenosine triphosphate; Autophagy; Biosynthesis; Care and treatment; Cyclic AMP-dependent protein kinases; Development and progression; Dopamine; Endoplasmic reticulum; Enzymes; Health aspects; Homeostasis; Insects; Kinases; Membrane separation; Mitochondria; Mutation; Neurons; Oxidative stress; Parkinson disease; Parkinson's disease; Phosphorylation; Physiological aspects; Proteins
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/1673-5374.213546

AMP-activated protein kinase (AMPK), a serine/threonine kinase, is a well-known intracellular master energy sensor whose activity is tightly linked to the level of adenosine monophosphate (AMP) and adenosine triphosphate (ATP) in the cell. Interestingly, PD gene mutations tend to result in dysregulation of these processes, suggesting that AMPK is a potential therapeutic target for PD. Indeed, pharmacological activators of AMPK such as 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and Metformin exhibit some success in improving Parkinsonian phenotypes in experimental and toxin-induced models of PD although conflicting results pointing towards the detrimental effects of AMPK activation were also observed. Alternatively, AMPK can activate mitochondrial fission during autophagy induction through phosphorylating Mff and recruitment of Drp1 (Toyama et al., 2016). [...]AMPK plays a Janus-like role in regulating mitochondrial fission. {Figure 2} Three separate studies also further established that transcriptional repression of PGC-1α as a mechanism underlying neurotoxin effects and neuroinflammation in PD. Siddiqui et al. in 2012 reported that mitochondrial toxin manipulates mitochondrial biogenesis in 2 ways, increasing α-syn-dependent repression as well as decreasing myocyte enhancer factor 2C (MEF2C)-mediated transcription of PGC-1α, with oxidative stress exerting a synergistic effect.