Chapter 9. Therapeutical implications of melatonin in Alzheimer´s and Parkinson´s diseases.

CARDINALI DP; VIGO DE; OLIVAR N; VIDAL MF; BRUSCO LI

TryptophanMetabolism: Implications for Biological Processes,Health andDisease

Springer

Lugar: New York; Año: 2015; p. 197 - 238

Neurodegenerative diseases like Alzheimer?s disease(AD) and Parkinson?s disease (PD) are major health problems, and a growingrecognition exists that efforts to prevent them must be undertaken by bothgovernmental and nongovernmental organizations. In this context, the pinealproduct melatonin has a promising significance because of itschronobiotic/cytoprotective properties. One of the features of advancing age isthe gradual decreas in endogenous melatonin synthesis. A limited number oftherapeutic trials have inicated that melatonin has a potential therapeuticvalue as a neuroprotective drug in the treatment of AD, minimal cognitiveimpairent (which may evolve to AD), and PD. Both in vitro and in vivo, melatoninprevented the neurodegeneration seen in experimental models of AD and PD. Forthese effects to occur, doses of melatonin about two orders of magnitude higherthan those required to affect sleep and circadian rhythmicity are needed. Morerecently, attention has been focused on the development to potent melatoninanalogs with proonged effets which were employed in clinical trials insleep-disturbed or depressed patients in doses considerably higher than thoseemployed for melatonin. In view that the relative potencies of the analogs arehigher that that of the natural compound, clinical trials employing melatoninin the range of 50-100 mg/day are needed to assess its therapeutic validity inneurodegenerative disorders