Neurotrophic Factors as a Protective Strategy in Parkinsons Disease

Maria      Jose Diogenes; Tiago      Fleming Outeiro

Abstract

Neurodegenerative disorders are devastating human diseases that include Parkinsons, Huntingtons, Alzheimers, amyotrophic lateral sclerosis, and the frontal temporal dementias. Although the clinical manifestations of these disorders have been known for quite some time, our understanding of the molecular underpinnings is only starting to emerge. Protein misfolding and aggregation is a common hallmark among these diseases, and produce a number of cellular and functional alterations. The loss of dopaminergic neurons in the substantia nigra justified the use of dopaminergic therapies in patients. However, these strategies do not appear to confer disease-modifying effects, and do not prevent progression. The idea that neurotrophic factors might promote cell survival is an attractive one. Existing evidence from clinical trials is currently inconclusive, but some patients display clear clinical benefits. Thus, the current challenge is to develop novel strategies that make the use of neurotrophic factors more consistent.

Keywords: Parkinson's disease, protein misfolding, neurodegeneration, neurotrophins, brain-derived neurotrophic factor, glial cell line derived neurotrophic factor, se, protein misfolding, neurodegeneration, neurotrophins, brain-derived neurotrophic factor, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, frontal temporal dementias, parkinsonism, BDNF, GDNF, NGF, (MAPK) pathway, neurturin, neublastin, enovin, persephin, (PSPN), TrK-mediated neurotrophin signaling, hyponatremia, Unified Parkinson's Disease Rating Scale, UPDRS, dyskinesias, L-Dopa-induced dyskinesias