Document Detail


New synaptic and molecular targets for neuroprotection in Parkinson's disease.
MedLine Citation:
PMID:  22927178     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paolo Calabresi; Massimiliano Di Filippo; Antongiulio Gallina; Yingfei Wang; Jeannette N Stankowski; Barbara Picconi; Valina L Dawson; Ted M Dawson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-08-23
Journal Detail:
Title:  Movement disorders : official journal of the Movement Disorder Society     Volume:  28     ISSN:  1531-8257     ISO Abbreviation:  Mov. Disord.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-02-07     Completed Date:  2013-08-21     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  8610688     Medline TA:  Mov Disord     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-60     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Movement Disorders Society.
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MeSH Terms
Descriptor/Qualifier:
Humans
Neurons / drug effects*,  pathology
Neuroprotective Agents / therapeutic use*
Parkinson Disease* / drug therapy,  genetics,  pathology
Protein-Serine-Threonine Kinases / genetics,  metabolism
Receptor, Adenosine A2A / metabolism
Receptors, Dopamine / metabolism
Receptors, N-Methyl-D-Aspartate / metabolism
Signal Transduction / drug effects
Synapses / drug effects*,  pathology
Grant Support
ID/Acronym/Agency:
P50 NS038377/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Receptor, Adenosine A2A; 0/Receptors, Dopamine; 0/Receptors, N-Methyl-D-Aspartate; EC 2.7.11.1/LRRK2 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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