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Endocannabinoids and Neurodegenerative Disorders: Parkinson’s Disease, Huntington’s Chorea, Alzheimer’s Disease, and Others

  • Javier Fernández-RuizEmail author
  • Julián Romero
  • José A. Ramos
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 231)

Abstract

This review focuses on the role of the endocannabinoid signaling system in controlling neuronal survival, an extremely important issue to be considered when developing new therapies for neurodegenerative disorders. First, we will describe the cellular and molecular mechanisms, and the signaling pathways, underlying these neuroprotective properties, including the control of glutamate homeostasis, calcium influx, the toxicity of reactive oxygen species, glial activation and other inflammatory events; and the induction of autophagy. We will then concentrate on the preclinical studies and the few clinical trials that have been carried out targeting endocannabinoid signaling in three important chronic progressive neurodegenerative disorders (Parkinson’s disease, Huntington’s chorea, and Alzheimer’s disease), as well as in other less well-studied disorders. We will end by offering some ideas and proposals for future research that should be carried out to optimize endocannabinoid-based treatments for these disorders. Such studies will strengthen the possibility that these therapies will be investigated in the clinical scenario and licensed for their use in specific disorders.

Keywords

Alzheimer’s disease Cannabinoids Endocannabinoids Huntington’s disease Neurodegeneration Neuroprotection Parkinson’s disease 

Abbreviations

2-AG

2-Arachidonoyl-glycerol

3NP

3-Nitropropionate

5HT1A

Serotonin 1A receptor type

AD

Alzheimer’s disease

AEA

Anandamide

AMPA

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

BACE1

β-site amyloid precursor protein cleaving enzyme 1

BBB

Blood brain barrier

CAG

Cytosine-adenine-guanine

CB

Cannabinoid

CB1

Cannabinoid receptor type 1

CB2,

Cannabinoid receptor type 2

CBD

Cannabidiol

CBN

Cannabinol

CNS

Central Nervous System

COX-2

Cyclooxygenase-2

DAGL

Diacylglycerol lipase

eCB

Endocannabinoid

FAAH

Fatty acid amide hydrolase

HD

Huntington’s disease

HU-211

Dexanabinol

IL-10

Interleukin-10

iNOS

Inducible nitric oxide synthase

LPS

Lipopolysaccharide

MAGL

Monoacylglycerol lipase

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NADPH

Nicotinamide adenine dinucleotide phosphate

NMDA

N-methyl-D-aspartate

PD

Parkinson’s disease

PPAR

Peroxisome proliferator-activated receptor

ROS

Reactive oxygen species

SCA

Spinocerebellar ataxia

TNF-α

Tumor necrosis factor-α

TRPV1

Transient receptor potential vanilloid type 1

Δ9-THC

Δ9-tetrahydrocannabinol

Δ9-THCV

Δ9-tetrahydrocannabivarin

Notes

Acknowledgements

This work was supported by grants from CIBERNED (CB06/05/0089), MINECO (SAF2012/39173), and CAM (S2011/BMD-2308).

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Javier Fernández-Ruiz
    • 1
    • 2
    • 3
    Email author
  • Julián Romero
    • 4
    • 5
  • José A. Ramos
    • 1
    • 2
    • 3
  1. 1.Facultad de Medicina, Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en NeuroquímicaUniversidad ComplutenseMadridSpain
  2. 2.Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)MadridSpain
  3. 3.Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)MadridSpain
  4. 4.Laboratorio de Apoyo a la InvestigaciónHospital Universitario Fundación AlcorcónMadridSpain
  5. 5.Departamento de Ciencias BiosanitariasUniversidad Francisco de VitoriaMadridSpain

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