The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases

Autor: Heike Wulff, April L. Garing, Jenny Lam, Nichole Coleman
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Parkinson's disease
Small-Conductance Calcium-Activated Potassium Channels
Clinical Biochemistry
small-conductance
Neurodegenerative
chemistry.chemical_compound
Alcohol Use and Health
Substance Misuse
Drug Discovery
2.1 Biological and endogenous factors
Aetiology
Mental Disorders
NS13001
KCa2
Afterhyperpolarization
Neurodegenerative Diseases
Pharmacology and Pharmaceutical Sciences
Alzheimer's disease
alcohol dependence and withdrawal
riluzole
Riluzole
Alcoholism
medicine.anatomical_structure
SKA-31
Neurological
Molecular Medicine
Mental health
medicine.symptom
learning and memory
medicine.drug
medicine.medical_specialty
Ataxia
Artificial Intelligence and Image Processing
Central nervous system
Apamin
Article
calcium-activated potassium channel
Membrane Transport Modulators
medicine
Genetics
Animals
Humans
Oncology & Carcinogenesis
Psychiatry
Pharmacology
Episodic ataxia
Cerebellar ataxia
business.industry
ataxia
Neurosciences
medicine.disease
Brain Disorders
schizophrenia
NS309
Good Health and Well Being
chemistry
business
apamin
EBIO
afterhyperpolarization
Zdroj: Lam, J; Coleman, N; Garing, ALA; & Wulff, H. (2013). The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases. Expert Opinion on Therapeutic Targets, 17(10), 1203-1220. doi: 10.1517/14728222.2013.823161. UC Davis: Retrieved from: http://www.escholarship.org/uc/item/4zp6694g
Expert opinion on therapeutic targets, vol 17, iss 10
DOI: 10.1517/14728222.2013.823161.
Popis: Introduction: KCa2 or small-conductance Ca2+-activated K+channels (SK) are expressed in many areas of the central nervous system where they participate in the regulation of neuronal afterhyperpolarization and excitability, and also serve as negative feedback regulators on the glutamate-NMDA pathway. Areas covered: This review focuses on the role of KCa2 channels in learning and memory and their potential as therapeutic targets for Alzheimer's and Parkinson's disease, ataxia, schizophrenia and alcohol dependence. Expert opinion: There currently exists relatively solid evidence supporting the use of KCa2 activators for ataxia. Genetic KCa2 channel suppression in deep cerebellar neurons induces ataxia, while KCa2 activators like 1-EBIO, SKA-31 and NS13001 improve motor deficits in mouse models of episodic ataxia (EA) and spinal cerebellar ataxia (SCA). Use of KCa2 activators for ataxia is further supported by a report that riluzole improves ataxia in a small clinical trial. Based on accumulating literature evidence, KCa2 activators further appear attractive for the treatment of alcohol dependence and withdrawal. Regarding Alzheimer's disease, Parkinson's disease and schizophrenia, further research, including long-term studies in disease relevant animal models, will be needed to determine whether KCa2 channels constitute valid targets and whether activators or inhibitors would be needed to positively affect disease outcomes. © Informa UK, Ltd.
Databáze: OpenAIRE
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