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.
Highlights
The pathology of Parkinson’s disease (PD) involves chronic degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc)
Prominent pathological manifestations associated with degeneration of SNc DAergic neurons include observations describing mitochondrial abnormalities [1,2,3,4], excessive cytosolic dopamine (DA) oxidation, α-synuclein aggregates, autophagolysosome dysfunction, defects in the ubiquitin-proteasome system (UPS), oxidative stress, nitrosative stress, iron released from bound storage and a gradual loss of neuromelanin (NM) [5,6,7]
While gradual loss of DAergic SNc pigmented cells occur as a natural process of aging—early diagnosis of PD is associated with a 30%/60% reduction of DAergic neurons/striatal DA which is attributable to degeneration of striatal axon terminals [14]
Summary
The pathology of Parkinson’s disease (PD) involves chronic degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). Prominent pathological manifestations associated with degeneration of SNc DAergic neurons include observations describing mitochondrial abnormalities [1,2,3,4], excessive cytosolic dopamine (DA) oxidation, α-synuclein aggregates, autophagolysosome dysfunction, defects in the ubiquitin-proteasome system (UPS), oxidative stress, nitrosative stress, iron released from bound storage and a gradual loss of neuromelanin (NM) [5,6,7]. Chronic SNc DAergic degeneration parallels a reduction of [18]F-DOPA uptake and DAT binding which are foundational events to faulty circuitry in the basal ganglia that triggers locomotive disability [31]
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