CNS & Neurological Disorders - Drug Targets

(Formerly Current Drug Targets - CNS & Neurological Disorders)

Stephen D. Skaper  
Department of Pharmaceutical and Pharmacological Sciences
University of Padova
Padova
Italy

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

Author(s): Marcelo M.S. Lima, Adriano D.S. Targa, Ana C.D. Noseda, Lais S. Rodrigues, Ana Marcia Delattre, Fabiola V. dos Santos, Mariana H. Fortes, Maira J. Maturana, Anete 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 PD 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 may exert reciprocal regulation hence; hypoinsulinemia induced by streptozotocin decreased the amounts of dopamine transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta. Accordingly, dopamine 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 peroxisome proliferator-activated receptor-γ, ATP-sensitive K+ channels, AMP-activated protein kinase, glucagon-like peptide-1 and dipeptidyl peptidase-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.

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Article Details

VOLUME: 13
ISSUE: 3
Year: 2014
Page: [418 - 428]
Pages: 11
DOI: 10.2174/18715273113126660155
Price: $58