Multi-target Drug Treatments for Neurodegenerative Disease

Dear Colleagues,

Degeneration of the central nervous system (CNS) is characterized by chronic progressive loss of the structure and functions of neuronal materials, resulting in functional and mental impairments. While the causes associated with neuronal degeneration remain poorly understood, the incidence of neurodegeneration increases with age, and it is most common in mid-to-late adult life. Neurodegenerative diseases share a range of molecular and cellular pathologies, including protein aggregation, mitochondrial dysfunction, glutamate toxicity, calcium load, proteolytic stress, oxidative stress, neuroinflammation, and aging, which contribute to neuronal death. Current therapies for neurodegenerative disorders treat symptoms and final manifestations, including aggregate build-up, memory loss, behavioral changes, and sleep deficits; however, this strategy is not a sustainable approach to the management of disease onset or progression. One promising approach considers the inhibition of amyloid formation by small-molecule inhibitors; however, the failure of multiple clinical therapeutic approaches indicates that the current strategies must be modulated and the importance of targeting pre-symptomatic signs, such as oxidative stress and inflammation, must be emphasized. Both oxidative stress and neuroinflammation precede over the symptomology of neurodegenerative disorders, and each promotes a neurotoxic environment associated with neurodegeneration.

In this scenario, polyphenols represent a promising starting point for new preventive and therapeutic approaches, since they effectively and simultaneously target epigenetic, metabolic, inflammatory, and oxidative pathways, as well as amyloid aggregation. These molecules have global availability, low cost, and low toxicity. Improved knowledge of these topics is essential in promoting the use of natural polyphenols far beyond their known antioxidant, antidiabetic, and antilipidemic effects. Increased information on this topic could be exploited to enrich, from a commercial and nutraceutical point of view, the alimentary and healthy values of natural compounds.

Dr. Manuela Leri
Dr. Marzia Vasarri
Guest Editors

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