Title:Role of Neurotrophic Factors in Parkinson's Disease
Volume: 23
Issue: 5
Author(s): Diogo Tome, Carla Pais Fonseca, Filipa Lopes Campos and Graca Baltazar
Affiliation:
Keywords:
Parkinson's disease, neurotrophic factors, dopaminergic neurons, BDNF, GDNF, neuroprotection, therapy.
Abstract: Parkinson’s disease is an age-associated progressive neurodegenerative disorder that has gained crescent
social and economic impact due to the aging of the western society. All current therapies are symptomatic
and fail to reverse or halt the progression of dopaminergic neurons loss. The discovery of the capability of neurotrophic
factors to protect these neurons lead numerous research groups to focus their efforts in developing
therapies aiming at promoting the control of Parkinson´s disease through the delivery of neurotrophic factors to
the brain or by boosting their endogenous levels. Both strategies were successful in inducing protection of dopaminergic
neurons and motor recovery in preclinical models of the disease. Contrariwise, very limited success was
obtained in clinical studies, where glial cell line-derived neurotrophic factor and neurturin were the neurotrophic
factors of choice for Parkinson’s disease therapy. These drawbacks motivate the development of novel forms of
delivery or the modification of the injected molecules aiming at providing a more stable and effective administration
with improved diffusion in the target tissue, and without the immune responses observed in the earliest clinical
studies. Although promising results were obtained with some of these new approaches performed in experimental
models of the disease, they were not yet tested in human studies. In this review, we present the current
knowledge on neurotrophic factors and their role in Parkinson’s disease, focusing on the strategies that have been
developed to increase their levels in target areas of the brain to achieve protection of dopaminergic neurons and
motor behaviour recovery.
