Neuroprotective gene therapy in the aging brain

Aging is associated with a progressive increase in the incidence of neurodegenerative diseases in both laboratory animals and humans. In the central nervous system, cholinergic and dopaminergic (DA) neurons are among the cells most susceptible to the deleterious effects of age. Thus, the basal forebrain cholinergic system is known to undergo moderate neurodegenerative changes during normal aging as well as severe atrophy in Alzheimer’s disease (AD). Parkinson's disease (PD), a degeneration of nigro-striatal DA neurons is the most conspicuous reflection of the vulnerability of DA neurons to age. Overall, there is growing evidence that a progressive decline in cognitive function and central DA activity represents basic features of normal aging both in humans and laboratory rodents. Exacerbation of these processes contributes to the symptoms of AD and PD, respectively. In this context, neurotrophic factors that can prevent or delay the decline in cognitive function and central DA activity during normal aging may reveal new therapeutic avenues for treatment of AD and PD and are therefore of clinical interest. Among the peptide factors, Insulin-like Growth Factor I (IGF-I) and Glial cell line-Derived Neurotrophic Factor are emerging as powerful neuroprotective molecules for the treatment of neurodegenerative pathologies. Among the neurosteroids, estrogens are recognized as neuroprotective and seem to act synergistically with IGF-I and possibly other neurotrophic peptides. This chapter will discuss the evidence supporting the neuroprotective relevance of the above factors.
Instituto de Investigaciones Bioquímicas de La Plata