MovDisordV3, Main, Exploration, bibRecord, 000738

The genetics of Parkinson’s disease: progress and therapeutic implications

Identifieur interne : 000738 ( Main/Exploration ); précédent : 000737; suivant : 000739

The genetics of Parkinson’s disease: progress and therapeutic implications

Auteurs : Andrew B. Singleton [États-Unis] ; Matthew J. Farrer [Canada] ; Vincenzo Bonifati [Pays-Bas]

Source :

Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2013.

RBID : PMC:3578399

English descriptors

KwdEn :
- Disease Progression, Genetic Predisposition to Disease (genetics), Humans, Mutation (genetics), Nerve Tissue Proteins (genetics), Parkinson Disease (etiology), Parkinson Disease (genetics), Parkinson Disease (therapy), Protein-Serine-Threonine Kinases (genetics), alpha-Synuclein (genetics).
MESH :
- chemical , genetics : Nerve Tissue Proteins, Protein-Serine-Threonine Kinases, alpha-Synuclein.
- etiology : Parkinson Disease.
- genetics : Genetic Predisposition to Disease, Mutation, Parkinson Disease.
- therapy : Parkinson Disease.
- Disease Progression, Humans.

Abstract

The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson’s disease (PD). Notably, while most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2, has been found to be common in certain populations.

There has been considerable progress in finding risk loci. To date approximately 16 such loci exist, notably some of these overlap with the genes known to contain disease-causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise second generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD.

The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis, by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics; notably via the reduction and clearance of α-synuclein and inhibition of Lrrk2 kinase activity.

We believe this has been an exciting and productive time for PD genetics, and furthermore, that genetics will continue to drive the etiologic understanding and etiology based therapeutic approaches in this disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578399

DOI: 10.1002/mds.25249
PubMed: 23389780
PubMed Central: 3578399

Affiliations:

Canada, Pays-Bas, États-Unis

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p id="P1">The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson’s disease (PD). Notably, while most mutations, such as those in <italic>SNCA, PINK1</italic>
, <italic>PARK2</italic>
, <italic>PARK7</italic>
, <italic>PLA2G6</italic>
, <italic>FBXO7</italic>
, and <italic>ATP13A2</italic>
, are a rare cause of disease, one particular mutation in <italic>LRRK2</italic>
, has been found to be common in certain populations.</p>
<p id="P2">There has been considerable progress in finding risk loci. To date approximately 16 such loci exist, notably some of these overlap with the genes known to contain disease-causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise second generation sequencing methods have facilitated the identification of new mutations in <italic>PD</italic>
. These methods will continue to provide novel insights into PD.</p>
<p id="P3">The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis, by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics; notably via the reduction and clearance of α-synuclein and inhibition of Lrrk2 kinase activity.</p>
<p id="P4">We believe this has been an exciting and productive time for PD genetics, and furthermore, that genetics will continue to drive the etiologic understanding and etiology based therapeutic approaches in this disease.</p>
</div>
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Movement Disorders (revue)

The genetics of Parkinson’s disease: progress and therapeutic implications

The genetics of Parkinson’s disease: progress and therapeutic implications

Source :

English descriptors

Abstract

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	Movement Disorders (revue)
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