Neurotrophic factors and neurodegenerative diseases: a delivery issue.

Neurotrophic factors (NTFs) represent one of the most stimulating challenge in neurodegenerative diseases, due to their potential in neurorestoring and neuroprotection. Despite the large number of proofs-of-concept and evidences of their activity, most of the clinical trials, mainly regarding Parkinson's disease and Alzheimer's disease, demonstrated several failures of the therapeutic intervention. A large number of researches were conducted on this hot topic of neuroscience, clearly evidencing the advantages of NTF approach, but evidencing the major limitations in its application. The inability in crossing the blood-brain barrier and the lack of selectivity actually represent some of the most highlighted limits of NTFs-based therapy. In this review, beside an overview of NTF activity versus the main neuropathological disorders, a summary of the most relevant approaches, from invasive to noninvasive strategies, applied for improving NTF delivery to the central nervous systems is critically considered and evaluated.