Somatostatin and Alzheimer's disease.
Alzheimer's disease (AD) is characterized by the cerebral deposition of senile plaques that are mainly composed of a set of peptides referred to as amyloid beta-peptides (Abeta). Among the numerous neuropeptides produced in intrinsic cortical and hippocampal neurons, somatostatin (SRIF) has been found to be the most consistently reduced in the brain and cerebrospinal fluid of AD patients. SRIF receptors (SSTR), which mediate the neuromodulatory signals of SRIF, are also markedly depleted in the AD brain, there being subtype-selective alterations in cortical areas. In the rat temporal cortex, we have shown that intracerebroventricular infusion of Abeta25-35 results in a decrease in SRIF-like immunoreactivity and in SRIF receptor subtype 2 (SSTR2) mRNA and protein levels, in correlation with a decrease in SSTR functionality. Insulin-like growth factor-I prevents the reduction in these parameters induced by Abeta25-35. Abeta has recently been demonstrated to be degraded primarily by a neutral endopeptidase, neprilysin, in the brain. SRIF regulates brain Abeta levels via modulation of neprilysin activity. Because SRIF expression in the brain declines upon aging in various mammals, including rodents, apes and humans, the aging-dependent reduction of SRIF has been hypothesized to trigger accumulation of Abeta in the brain by suppressing neprilysin action. Here we present an overview of recent advances on the role of SRIF in AD and its relationship with Abeta peptides.
Burgos-Ramos
E
E
Unidad de Neurobioquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain.
Hervás-Aguilar
A
A
Aguado-Llera
D
D
Puebla-Jiménez
L
L
Hernández-Pinto
A M
AM
Barrios
V
V
Arilla-Ferreiro
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004798:Enzymes / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism
D016229:Amyloid beta-Peptides; D004798:Enzymes; C088485:Neprolyzin; D017481:Receptors, Somatostatin; C115977:Sstr2 protein, rat; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D000262:Adenylyl Cyclases