Old and new evidence for neuropeptide involvemeint in alzheimer's disease

Alzheimer's disease (AD) is an irreversible degenerative disorder characterized by degeneration of neurons in different areas and by progressive cognitive and fictional decline. Various deranged mechanism play a role in the disease process all inducing neuronal death, the inevitable event occurring in AD. Novel therapeutic approaches using disease-modifying treatment are being investigated with the intention of influencing multiple pathways involved in AD. Because of they putative roles as neurotransmitters, neuromodulators and neuroregulators in the central nervous system, neuropeptides have been the object of considerable research. Postmortem studies have provided evidence that several neuropeptide-containing neurons are pathologically altered in brain areas of AD patient, as well as in brain of animal model of AD: In addition, altered levels of neuropeptides have been found in cerobrospinal fluid (CSF) of AD patients, getting insight into the potential role of neuropeptides in the pathophysiology of AD and offering the possibility to identify novel biomarkers of this pathology. The role exerted by neuropeptides seems particularly interesting since they are generally neuroprotective and widely distributed in brain areas responsible for learning and memory processes. The present review summarizes the recent finding on neuropeptide involved in AD, with the focus on the contribution of thyrotrophin-releasing hormone, cholecystokinin, bradikinin and chomogranin/secretogranin family, describing brain distribution and the role played in AD and cognitive function, as well as their neuroprotective properties. Convincing evidence has been provided for the protective role of these neuropepides against neurodegeneration observed in AD, both in vitro an in vivo, identifying neuropetide receptors as potential therapeutic target