Browsing by Subject "Myelin"

Now showing 1 - 4 of 4
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    Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics
    (BMC, 2022-10-26) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
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    Myelin repair in Alzheimer's disease: a review of biological pathways and potential therapeutics
    (Springer, 2022-10-26) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of Alzheimer's disease (AD). We discuss previously investigated therapeutic targets of amyloid, tau, and ApoE, as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD. Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation, maturation, and myelin production. There is a present need for a single, cohesive model of myelin homeostasis in AD. While determining a causative pathway is beyond the scope of this review, it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.
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    Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro-myelinating genes
    (Wiley, 2021-06) Huff, Tyler C.; Sant, David W.; Camarena, Vladimir; Van Booven, Derek; Andrade, Nadja S.; Mustafi, Sushmita; Monje, Paula V.; Wang, Gaofeng; Neurological Surgery, School of Medicine
    Ascorbic acid (vitamin C) is critical for Schwann cells to myelinate peripheral nerve axons during development and remyelination after injury. However, its exact mechanism remains elusive. Vitamin C is a dietary nutrient that was recently discovered to promote active DNA demethylation. Schwann cell myelination is characterized by global DNA demethylation in vivo and may therefore be regulated by vitamin C. We found that vitamin C induces a massive transcriptomic shift (n = 3,848 genes) in primary cultured Schwann cells while simultaneously producing a global increase in genomic 5-hydroxymethylcytosine (5hmC), a DNA demethylation intermediate which regulates transcription. Vitamin C up-regulates 10 pro-myelinating genes which exhibit elevated 5hmC content in both the promoter and gene body regions of these loci following treatment. Using a mouse model of human vitamin C metabolism, we found that maternal dietary vitamin C deficiency causes peripheral nerve hypomyelination throughout early development in resulting offspring. Additionally, dietary vitamin C intake regulates the expression of myelin-related proteins such as periaxin (PRX) and myelin basic protein (MBP) during development and remyelination after injury in mice. Taken together, these results suggest that vitamin C cooperatively promotes myelination through 1) increased DNA demethylation and transcription of pro-myelinating genes, and 2) its known role in stabilizing collagen helices to form the basal lamina that is necessary for myelination.
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    White Matter Microstructural Changes in the Cingulum Bundle of the Hippocampus in Alzheimer's Disease
    (2023-07) Hirschfeld, Lauren Rose; Risacher, Shannon L.; Saykin, Andrew J.; Block, Michelle L.; Wu, Yu-Chien; Nho, Kwangsik; Cao, Sha
    Alzheimer’s disease (AD), the most common dementia, is the seventh leading cause of death for adults in the US. Recent FDA-approved therapeutics targeting hallmark amyloid pathology may slow but do not yet halt the disease. Thus, it is likely that other factors, such as neurodegeneration, play a role in disease development. Compromised white matter (WM) microstructural integrity may be a promising biomarker for disease progression, as it has been demonstrated in both preclinical and clinical AD. WM microstructural changes can be estimated using diffusion tensor imaging (DTI), a noninvasive imaging modality which measures the diffusion of water molecules within brain tissue. First, literature describing a biological relationship between signaling pathways involved in both insufficient myelin-repair mechanisms and AD pathology was assessed to establish a foundation for studying WM in the context of AD. Then, DTI was used to assess possible WM microstructural changes of the cingulum bundle of the hippocampus (CBH), a disease-relevant region, in the KBASE cohort of older Korean adults on the AD continuum. Similar to White cohorts of European ancestry, DTI values corresponding to worsening WM microstructure occurred in a stepwise fashion across diagnostic stages and were associated with both cognition and amyloid deposition. In a sample of older adults from the Indiana Memory and Aging Study (IMAS), CBH microstructure was a sensitive biomarker of preclinical conversion from cognitively unimpaired status to mild cognitive impairment. Finally, a novel extension of the T1/T2 weighted ratio imaging method, thought to estimate myelin- related tissue integrity, yielded values in IMAS subjects reflective of previously observed DTI patterns. The complex interplay between amyloid, tau, and neurodegeneration in AD is not yet fully characterized. This research shows decreased integrity of WM microstructure in the CBH, which may be useful as a biomarker of early disease conversion to MCI.