Current Drugs and Potential Future Neuroprotective Compounds for Parkinson's Disease

Abstract

The research progress of understanding the etiology and pathogenesis of Parkinson's disease (PD) has yet lead to the development of some clinical approaches intended to treat cognitive and behavioral symptoms, such as memory and perception disorders. Despite the major advances in different genetic causes and risk factors for PD, which share common pathways to cell dysfunction and death, there is not yet a complete model of PD that can be used to accurately predict the effect of drugs on disease progression. Clinical trials are also important to test any novel neuro-protective agent, and recently there have been great advances in the use of anti-inflammatory drugs and plant flavonoid antioxidants to protect against specific neuronal degeneration and its interference with lipid and cholesterol metabolism. The increasing knowledge of the molecular events underlying the degenerative process of PD has stimulated research to identify natural compounds capable of halting or slowing the progress of neural deterioration. Polyphenols and flavonoids, which play a neuroprotective role in a wide array of in vitro and in vivo models of neurological disorders, emerged from among the multi-target bio-agents found mainly in plants and microorganisms. This review presents a detailed overview of the multimodal activities of neuroprotective bio-agents tested so far, emphasizing their neurorescue/neuroregenerative activity. The brain-penetrating property of bioagents may make these compounds an important class of natural drugs for the treatment of neurodegenerative diseases. Although there are numerous studies demonstrating beneficial effects in the laboratory by identifying critical molecular targets, the clinical efficacy of these neuroprotective treatments remains to be proven accurately.

Keywords: Parkinson's disease; degeneration; neuroprotection; neuroscience; nutraceuticals; phytobioactivity..

Fig. (1)

Comparative dopaminergic immunoreactivity effects of AtreMorine against PD pathology. Comparative photomicrographs of dopaminergic immunoreactivity (TH) of the substantia nigra pars compacta (SNpc) of MPTP-induced mice with different treatments. Transverse brain sections of mice from groups treated with PBS (control), AtreMorine only [10.5% ([20%]; CI 8.3–12.6%; p<0.001)] and the combination of AtreMorine and synthetic L-DOPA [24.5% ([50%]; CI 21.1–28.0%; p<0.001)], showing the remarkable neuroprotective effect of AtreMorine treatment by reducing the dopaminergic degeneration in the SNpc neurons. Comparative sections show a notable neuroprotection effect of AtreMorine in mice when compared with control mice [31.8% ([60%]; CI 29.0–34.3%; p<0.015)]. Scale bar: 100 µm. (The color version of the figure is available in the electronic copy of the article).