I spent a great deal of time this past week investigating the organic chemistry dynamics of the ACS study Mechanistic Insights into Polyphenols’ Aggregation Inhibition of α-Synuclein and Related Peptides. This study only examined the impact of resveratrol & gallic acid on the aggregation of α-synuclein & its results showed that rather than disrupting α-synuclein aggregation the polyphenols merely became weakening elements of a broadened sheet. Importantly, the narrow scope of this research excluded consideration of whether the toxicity to glial cells of this disease causing protein was lessened & their dutiful activities excited by the studied polyphenols.
Here I am interested in the vitality of glial mitochondria & their susceptiblity to problematic exposure mitophagy which requires having evidence of how the citric acid cycle for its energy production (ATP reservoir on/off switch) is affected by disease conditons.
…. more to come (Creative Commons image uploads await discussion & pairings)
Axial section through mid-brain. (Schematic.) (Testut.) 1. Corpora quadrigemina. 2. Cerebral aqueduct. 3. Central gray stratum. 4. Interpeduncular space. 5. Sulcus lateralis. 6. Substantia nigra. 7. Red nucleus of tegmentum. 8. Oculomotor nerve, with 8’, its nucleus of origin. a. Lemniscus (in blue) with a’ the medial lemniscus and a” the lateral lemniscus. b. Medial longitudinal fasciculus. c. Raphé. d. Temporopontine fibers. e. Portion of medial lemniscus, which runs to the lentiform nucleus and insula. f. Cerebrospinal fibers. g. Frontopontine fibers.
Brainstem nuclei involved in human emotion. (A) Sagittal view and (B) Coronal view. DR, Dorsal Raphe; LC, Locus coeruleus; LDT, Laterodorsal tegmental nucleus; Mb, Midbrain; MR, Median raphe; P, Pons; PAG, Periaqueductal gray; PBC, Parabrachial nuclear complex; PPN, Pedunculopontine nucleus; VTA, Ventral tegmental area. The substantia nigra and the nucleus of the tractus solitarius are not shown to optimize visibility of the other structures.
New Frontiers in Parkinson’s Research and Care
References 1. Zecca L. et all. Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour. Molecular Pathology 2001 Dec; 54(6): 414–418. 2. Friedrich et al. Cell specifc quantitative iron mapping on brain slices by immuno-µPIXE in healthy elderly and Parkinson’s disease. Acta Neuropathology Communications 2021 9:47 3. Haddad A et al. Biochemistry, Citric Acid Cycle. StatPearls Publishing; 2023 Jan 4. Metrani R et al. Comparative Metabolomics Profiling of Polyphenols, Nutrients and Antioxidant Activities of Two Red Onion (Allium cepa L.) Cultivars. Plants (Basel). 2020 Sep; 9(9): 1077. 5. Malpartida A et al. Mitochondrial Dysfunction and Mitophagy in Parkinson’s Disease: From Mechanism to Therapy. Trends in Biochemical Science. 2021 Apr; 46(4): 329-343 6. Festa B et al. Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration. Neuron. 2023 Apr. 7. Sukhorukov V et al. Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders. International Journal of Molecular Sciences. 2021 Sep 22(19). 8. Wong E et al. Mitophagy Transcriptome: Mechanistic Insights into Polyphenol-Mediated Mitophagy. Oxidative Medicine and Cellular Longevity. 2017 May. 9. Shields H et al. Beneficial and Detrimental Effects of Reactive Oxygen Species on Lifespan: A Comprehensive Review of Comparative and Experimental Studies. Frontiers in Cell and Developmental Biology. 2021 Feb 9.