Bringing natural products into the fold - exploring the therapeutic lead potential of secondary metabolites for the treatment of protein-misfolding-related neurodegenerative diseases

This review, citing 187 references, is an account of natural products exhibiting bioactive properties relevant to the treatment of protein aggregation-related neurodegenerative diseases (e. g., Huntington's, Parkinson's, and prion diseases). We have compared the chemical properties of secondary metabolite leads to compounds that are in current clinical use for treating central nervous system targets. This comparison revealed that natural products possess many of the desirable traits found in central nervous system-acting agents. It was also observed that the discovery of secondary metabolite leads from marine and microbial sources lags far behind the substantial discoveries emerging from plants. We have concluded this review by providing details concerning many of the most promising secondary metabolite leads that have been identified with therapeutic applications specific to the treatment of Huntington's, Parkinson's and prion diseases. We have also summarized compounds that have more generalized bioactivities that are favorable for treating a broad range of neurodegenerative disorders (i.e., anti-inflammatory, prevention of glutamate-induced neurotoxicity, neurotrophic activity, and inhibition of monoamine oxidase activity).