Parkinson's disease: mitochondrial molecular pathology, inflammation, statins, and therapeutic neuroprotective nutrition.
Pathological hallmarks of Parkinson's disease are destruction of dopaminergic neurons in the basal ganglia, especially the substantia nigra, and the presence of Lewy bodies within nerve cells. Environmental toxins are associated with the disease and, in a minority of cases, genetic factors have been identified. Inflammation-with activation of phagocytic microglia, release of cytokines, invasion by T cells, and complement activation-plays a role in damaging these neurons. Excessive production of reactive oxygen species, mitochondrial dysfunction leading to apoptosis, accumulation and oligomerization of the protein alpha-synuclein, and defective protein disposal by the ubiquitin proteasome system are involved in the complex web of events mediating nigral cell demise. Two agents of current interest, coenzyme Q10 and creatine, may be disease modifying, and large studies are in progress. Related mechanisms of other substances, including omega-3 fatty acids and vitamin D, are included in this review. The association with serum cholesterol levels and the effects of statin drugs are uncertain but important.
Kones
Richard
R
Cardiometabolic Research Institute, Houston, Texas, USA. drrkones@sbcglobal.net
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D003401:Creatine / Q000627:therapeutic use*; D004035:Diet Therapy; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D008928:Mitochondria / Q000502:physiology*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014807:Vitamin D / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D014815:Vitamins; D014451:Ubiquinone; D014807:Vitamin D; D002784:Cholesterol; C024989:coenzyme Q10; D003401:Creatine