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GSK-3 inhibitors: a ray of hope for the treatment of Alzheimer's disease?
J Alzheimers Dis. 2008 Oct; 15(2):181-91.JA

Abstract

Alzheimer's disease (AD) is the most common form of dementia affecting more than 15 millions individuals worldwide. While the cause is unknown, there are two major neuropathological abnormalities present in the brains of patients with AD, the extracellular senile plaques and the intracellular neurofibrillary tangles. There is strong evidence that glycogen synthase kinase-3 (GSK-3) plays an important role in AD being involved in the regulation of these neuropathological hallmarks. Increased activity and/or overexpression of this enzyme in AD is associated with increased tau hyperphosphorylation and alterations in amyloid-beta processing that are thought to precede the formation of neurofibrillary tangles and senile plaques, respectively. Furthermore, over activity of GSK-3 is also involved in neuronal loss. These data clearly identify GSK-3 inhibitors as one of the most promising new approaches for the future treatment of AD and a reduction of the aberrant over activity of this enzyme might decrease several aspects of the neuronal pathology in AD. In this review, we provide an overview of the rationale for the development of GSK-3 inhibitors for the treatment of AD, discussing the risks and benefits of this approach.

Authors+Show Affiliations

Instituto de Química Médica-CSIC, Madrid, Spain. amartinez@iqm.csic.esNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18953107

Citation

Martinez, Ana, and Daniel I. Perez. "GSK-3 Inhibitors: a Ray of Hope for the Treatment of Alzheimer's Disease?" Journal of Alzheimer's Disease : JAD, vol. 15, no. 2, 2008, pp. 181-91.
Martinez A, Perez DI. GSK-3 inhibitors: a ray of hope for the treatment of Alzheimer's disease? J Alzheimers Dis. 2008;15(2):181-91.
Martinez, A., & Perez, D. I. (2008). GSK-3 inhibitors: a ray of hope for the treatment of Alzheimer's disease? Journal of Alzheimer's Disease : JAD, 15(2), 181-91.
Martinez A, Perez DI. GSK-3 Inhibitors: a Ray of Hope for the Treatment of Alzheimer's Disease. J Alzheimers Dis. 2008;15(2):181-91. PubMed PMID: 18953107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GSK-3 inhibitors: a ray of hope for the treatment of Alzheimer's disease? AU - Martinez,Ana, AU - Perez,Daniel I, PY - 2008/10/28/pubmed PY - 2008/12/17/medline PY - 2008/10/28/entrez SP - 181 EP - 91 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 15 IS - 2 N2 - Alzheimer's disease (AD) is the most common form of dementia affecting more than 15 millions individuals worldwide. While the cause is unknown, there are two major neuropathological abnormalities present in the brains of patients with AD, the extracellular senile plaques and the intracellular neurofibrillary tangles. There is strong evidence that glycogen synthase kinase-3 (GSK-3) plays an important role in AD being involved in the regulation of these neuropathological hallmarks. Increased activity and/or overexpression of this enzyme in AD is associated with increased tau hyperphosphorylation and alterations in amyloid-beta processing that are thought to precede the formation of neurofibrillary tangles and senile plaques, respectively. Furthermore, over activity of GSK-3 is also involved in neuronal loss. These data clearly identify GSK-3 inhibitors as one of the most promising new approaches for the future treatment of AD and a reduction of the aberrant over activity of this enzyme might decrease several aspects of the neuronal pathology in AD. In this review, we provide an overview of the rationale for the development of GSK-3 inhibitors for the treatment of AD, discussing the risks and benefits of this approach. SN - 1387-2877 UR - https://www.unboundmedicine.com/medline/citation/18953107/GSK_3_inhibitors:_a_ray_of_hope_for_the_treatment_of_Alzheimer's_disease L2 - https://content.iospress.com/openurl?genre=article&issn=1387-2877&volume=15&issue=2&spage=181 DB - PRIME DP - Unbound Medicine ER -