If I was smarter, I might not be so excited about Niacin. I am pretty excited.
Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications 2019 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/
"Parkinson’s disease (PD) is a progressive disorder characterized by degeneration of dopaminergic neurons within the substantia nigra, whose main hallmarks are abnormal aggregation of the α-synuclein protein, inhibition of mitochondrial respiratory complex 1, oxidative stress and neuroinflammation. Because only 5–10% of PD cases can be ascribed to genetic predisposition, several environmental factors may play a role in sporadic forms of PD [149]. Among them, vitamin B3 is a promising preventive and therapeutic factor (Table 1), as it can alleviate certain types of early-onset PD symptoms. NAD+ levels, indeed, fall in patients with PD and, conversely, increasing niacin intake can increase dopamine synthesis in the striatum and restore optimal NAD+/NADH ratio needed for the activity of mitochondrial complex 1 [148]. High niacin levels can also sequester transition metal ions (including iron) that usually accumulate together with the occurrence of aggregated misfolded proteins [149,150]. Furthermore, optimal levels of vitamin B3 are needed for reducing oxidative stress and neuroinflammation, also implicated in PD pathogenesis: low doses of niacin alter macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenothype, while exogenous NADPH suppresses oxidative stress and glia-mediated neuroinflammation [151,152].
Neurons are the only cells of the brain expressing NNMT that seems to play an important role in sustaining neuron homeostasis [153]. Despite numerous investigations, the exact cause-effect relationship between NNMT and PD neuropathogenesis remains unclear. Some authors refer to NNMT as a risk factor for PD, since its levels are elevated in the cerebrospinal fluid and midbrain dopamine neurons of PD patients [153,154]. High NNMT activity is associated with low activity of mitochondrial complex 1, thus providing a link with mitochondrial dysfunction triggering neurodegeneration [154,155]. It is noteworthy that N1-methylnicotinamide (the metabolite generated by the action of NNMT) is structurally similar to N-methy-l-4-phenylpyridinium (MPP+), a toxin damaging dopamine neurons [168]. Conversely, other studies have demonstrated that the enzyme is able to (i) counteract the MPP+-mediated toxicity on mitochondrial complex 1, (ii) activate neuronal autophagy for balancing energy sources and cell homeostasis, and (iii) modulate neuron morphology and differentiation, by inducing neurite branching, synaptophysin expression and dopamine accumulation and release [156]. Likewise, NAD supplementation or inactivation of NAD-consuming enzymes [like PARP-1, a poly(ADP-ribose) polymerase involved in DNA repair] rescue mitochondrial defects and protect neurons against degeneration, in familial forms of PD characterized by mutations in the pink1 gene; this finding suggests that neurotoxicity associated with mitochondrial defects may be prevented by modulating NAD+ salvage metabolism in order to enhance NAD availability [169]."
Interesting table: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/table/ijms-20-00974-t001/?report=objectonly
Lots of digging to do.
