title: Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease.
abstract: This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson's disease (PD). Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation, but as an integral part of this process, superoxides and other reactive oxygen species are also produced. Excessive free radical production contributes to oxidative stress. Cells have evolved to handle such stress via various endogenous anti-oxidant proteins. One such family of proteins is the mitochondrial uncoupling proteins (UCPs), which are anion carriers located in the mitochondrial inner membrane. There are five known homologues (UCP1 to 5), of which UCP4 and 5 are predominantly expressed in neural cells. In a series of previous publications, we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium (MPP+; toxic metabolite of MPTP) and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential, and reducing oxidative stress. We also showed how their expression can be influenced by nuclear factor kappa-B (NF-κB) signaling pathway specifically in UCP4. Furthermore, we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin (hormone produced by adipocytes) acting via UCP2 against MPP+-induced toxicity. There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD. Their expression, which can be induced, may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.
authors.affiliation: Division of Neurology, Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China. slho@hku.hk.
authors.forename: Philip Wl
authors.initials: PW
authors.lastname: Ho
authors.forename: Jessica Wm
authors.initials: JW
authors.lastname: Ho
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Liu
authors.forename: Danny Hf
authors.initials: DH
authors.lastname: So
authors.forename: Zero Hm
authors.initials: ZH
authors.lastname: Tse
authors.forename: Koon-Ho
authors.initials: KH
authors.lastname: Chan
authors.forename: David B
authors.initials: DB
authors.lastname: Ramsden
authors.forename: Shu-Leong
authors.initials: SL
authors.lastname: Ho