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.
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 -