The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Abstract

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible.

Utilization Potentials of <i>Moringa oleifera</i> in Nigeria: A Preliminary Assessment

“…Nutraceuticals are food or components of food that provide medicinal or health benefits (Tapas et al, 2008). Dietary intake of flavonoids is used for the treatment of Parkinson disease (Mazzio et al, 2011). Clinical trials have linked increasing intake of flavonoids with a reduced occurrence of breast cancer in humans (Bosetti et al, 2005).…”

Free Radicals, Neuronal Death and Neuroprotection

“…Considering the cascade of degenerative events of diseases such as AD and PD (degradation and abnormal folding of proteins, inadequate energy production in CNS degeneration by oxidative damage, excitotoxicity and inflammation), there is interest in whether the AO, or changes in eating habits can prevent and/or block one or more of these pathways of neurodegeneration in slowing the progression of the disease (Mazzio, et al, 2011). In this regard, several studies have suggested some properties of antioxidants as protective factors against the risk of diseases such as AD and PD.…”

“…In addition, due to the critical role that these nutrients play in the metabolism of glucose and mitochondrial respiration justifies the use of B vitamins for patients with PD (Mazzio et al, 2011). Some authors argue that a relationship exists between the PD, vitamin B6, vitamin B12 and folic acid.…”

“…This relationship refers to the role played by these molecules in the regulation of homocysteine, since they are responsible for their cleavage to methionine and tetrahydrofolate. Such effects may attenuate the neurotoxicity associated with a condition known as hyperhomocysteinemia, which is associated with PD and cytotoxicity related Mitochondrial Transitory Permeability Pore (Mazzio et al, 2011). Additionally, it has been suggested that elevated levels of homocysteine may increase the severity of PD, since this amino acid could mediate neuronal toxicity through NMDA receptors, precipitating oxidative stress, calcium overload and apoptosis (Mazzio et al, 2011).…”

“…As mentioned above, the use of vitamin supplements may promote the biological integrity of systems, however, the combined use of vitamins and plant-derived polyphenolic compounds, seems to have good recognition as antioxidants (Mazzio et al, 2011). The use of supplements from plants to improve health is an issue that is gaining popularity among most people because it is considered that the use of natural products is safe and produces fewer side effects, compared to synthetic drug, in fact, to date over 50 different species of plants, and more than 8000 phenolic compounds have been identified with beneficial effects on health (Sun et al, 2008).…”