Volume 28, Issue 1 p. 51-60
Review

New synaptic and molecular targets for neuroprotection in Parkinson's disease

Paolo Calabresi MD

Corresponding Author

Paolo Calabresi MD

Clinical Neurology, University of Perugia, Perugia, Italy

IRCCS, Santa Lucia Foundation, Rome, Italy

Correspondence to: Professor Paolo Calabresi, Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, 06156 Perugia, Italy; [email protected]Search for more papers by this author
Massimiliano Di Filippo MD

Massimiliano Di Filippo MD

Clinical Neurology, University of Perugia, Perugia, Italy

IRCCS, Santa Lucia Foundation, Rome, Italy

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Antongiulio Gallina MD

Antongiulio Gallina MD

Clinical Neurology, University of Perugia, Perugia, Italy

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Yingfei Wang PhD

Yingfei Wang PhD

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Jeannette N. Stankowski PhD

Jeannette N. Stankowski PhD

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Barbara Picconi PhD

Barbara Picconi PhD

Clinical Neurology, University of Perugia, Perugia, Italy

IRCCS, Santa Lucia Foundation, Rome, Italy

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Valina L. Dawson PhD

Valina L. Dawson PhD

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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Ted M. Dawson MD, PhD

Ted M. Dawson MD, PhD

Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

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First published: 23 August 2012
Citations: 34

Funding agencies: This work was supported by grants from European Community contract number 222918 (REPLACES) FP7—Thematic priority HEALTH (PC), and Progetto Giovani Ricercatori Ministero Sanità 2008 (BP).

Relevant conflicts of interest/financial disclosures: Nothing to report.

Full financial disclosures and author roles may be found in the online version of this article.

Abstract

The defining anatomical feature of Parkinson's disease (PD) is the degeneration of substantia nigra pars compacta (SNc) neurons, resulting in striatal dopamine (DA) deficiency and in the subsequent alteration of basal ganglia physiology. Treatments targeting the dopaminergic system alleviate PD symptoms but are not able to slow the neurodegenerative process that underlies PD progression. The nucleus striatum comprises a complex network of projecting neurons and interneurons that integrates different neural signals to modulate the activity of the basal ganglia circuitry. In this review we describe new potential molecular and synaptic striatal targets for the development of both symptomatic and neuroprotective strategies for PD. In particular, we focus on the interaction between adenosine A2A receptors and dopamine D2 receptors, on the role of a correct assembly of NMDA receptors, and on the sGC/cGMP/PKG pathway. Moreover, we also discuss the possibility to target the cell death program parthanatos and the kinase LRRK2 in order to develop new putative neuroprotective agents for PD acting on dopaminergic nigral neurons as well as on other basal ganglia structures. © 2013 Movement Disorder Society