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CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)
ISSN (Print): 1871-5273
ISSN (Online): 1996-3181
Epub Full Text Article
DOI: 10.2174/18715273113126660155      Price:  $95









Does Parkinson’s Disease and Type-2 Diabetes Mellitus Present Common Pathophysiological Mechanisms and Treatments?

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Author(s): Lima MMS, Targa ADS, Noseda ACD, L S Rodrigues, A M Delattre, dos Santos FV, M H Fortes, M J Maturana and A C Ferraz
Abstract:
Parkinson’s disease (PD) is the second most common neurodegenerative disease afflicting about 1% of people over 65 years old and 4-5% of people over 85 years. It is proposed that a cascade of deleterious factors is set in motion within that neuron made not of one, but rather of multiple factors such as free radicals, excitotoxicity, neuroinflammation, and apoptosis to cite only some of the most salient. In this scenario, chronic systemic inflammation, as well as impaired mitochondrial metabolism, have also been suspected of playing a role in the development of type-2 diabetes, and the possibility of a shared pathophysiology of Parkinson’s disease and type-2 diabetes has been proposed. The discussion about the interactions between PD and type-2 diabetes mellitus began in the 1960’s and there is still controversy. Insulin and dopamine (DA) may exert reciprocal regulation hence; hypoinsulinaemia induced by streptozotocin decreased the amounts of DA transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta (SNpc). Accordingly, DA depletion in the striatum is able to decreases insulin signaling in basal ganglia, indicating that, perhaps, PD may be considered as a risk factor for the development of type-2 diabetes mellitus. In this sense, it is described that PPAR-, KATP, AMPK, GLP-1 and DPP-4 are important therapeutic targets for PD and reinforces the association with diabetes. Therefore, the objective of the present review is to contextualize the mutual pathophysiological interactions between PD and type-2 diabetes mellitus, as well as the potential common treatments
Keywords:
Dopamine, Treatment, Peroxisome proliferator-activated receptor-γ, Type-2 diabetes mellitus, Parkinson´s disease
Affiliation:
Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Fisiologia, Av. Francisco H. dos Santos s/n ZIP: 81.531 – 990, Caixa Postal: 19031, Curitiba – Paraná – Brasil