DOPA_B™ Alpha-synuclein blocker* Alpha-synuclein is a protein central to Parkinson’s disease (PD) pathogenesis, acting as the primary component of Lewy bodies and Lewy neurites, which are hallmark protein aggregates in the brain. Misfolded Alpha-synuclein accumulates and spreads, disrupting cellular functions, inducing neuronal death, and contributing to disease progression. [1, 2, 3, 4] Key Aspects of Alpha-synuclein in Parkinson’s Disease: Pathological Mechanism: Alpha-synuclein, normally a soluble protein involved in neurotransmitter release, misfolds into toxic oligomers and fibrils. These aggregated forms (Lewy bodies) accumulate in the brain, leading to the death of dopamine-producing neurons, specifically in the substantia nigra. Role in Disease: It is often referred to as the “culprit” in PD because its aggregation correlates with the motor and non-motor symptoms of the disease. [1, 2, 3, 4, 5, 6, 7, 8] Impact on Neuronal Function: The accumulation of Alpha-synuclein leads to mitochondrial dysfunction, oxidative stress, and impaired protein degradation pathways (like the autophagy-lysosome system), ultimately causing neuronal death. [9, 10] 1. Klein MO, Battagello DS, Cardoso AR, et al. Dopamine: Functions, Signaling, and Association with Neurological Diseases. Cell Mol Neurobiol. 2019 Jan;39(1):31-59. 2. Kumar MJ, Andersen JK. Perspectives on MAO-B in aging and neurological disease: where do we go from here? Mol Neurobiol. 2004 Aug;30(1):77-89. 3. Mazzio E, Deiab S, Park K, et al. High throughput screening to identify natural human monoamine oxidase B inhibitors. Phytother Res. 2013 Jun;27(6):818-28. 4. Zarmouh NO, Messeha SS, Elshami FM, et al. Natural Products Screening for the Identification of Selective Monoamine Oxidase-B Inhibitors. European J Med Plants. 2016 May;15(1). 5. Sun Y, Lenon GB, Yang AWH. Phellodendri Cortex: A Phytochemical, Pharmacological, and Pharmacokinetic Review. Evid Based Complement Alternat Med. 2019;2019:7621929. 6. Xian YF, Lin ZX, Ip SP, et al. Comparison the neuropreotective effect of Cortex Phellodendri chinensis and Cortex Phellodendri amurensis against beta-amyloid-induced neurotoxicity in PC12 cells. 2013 Jan 15;20(2):187-93. 7. Young-Pyo K, In-Chul, J. , & Sang-Ryong, L. Effects of Phellodendron amurense Extract on the Alzheimer’s Disease Model. Journal of Physiology & Pathology in Korean Medicine. 2005;19(1):130-8. 8. Schaffner A, Li X, Gomez-Llorente Y, et al. Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection. Cell Res. 2019 Apr;29(4):313-29. 9. Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry. 2007 Mar;64(3):327-37. 10. Ayano G. Dopamine: Receptors, Functions, Synthesis, Pathways, Locations and Mental Disorders: Review of Literatures. Journal of Mental Disorders and Treatment. 2016 01/01;2(2).