دورية أكاديمية
Warm, Sweetened Milk at the Twilight of Immunity - Alzheimer's Disease - Inflammaging, Insulin Resistance, M. paratuberculosis and Immunosenescence.
| العنوان: | Warm, Sweetened Milk at the Twilight of Immunity - Alzheimer's Disease - Inflammaging, Insulin Resistance, M. paratuberculosis and Immunosenescence. |
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| المؤلفون: | Dow CT; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2021 Aug 05; Vol. 12, pp. 714179. Date of Electronic Publication: 2021 Aug 05 (Print Publication: 2021). |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Disease Susceptibility* , Immunosenescence* , Insulin Resistance*, Alzheimer Disease/*etiology , Alzheimer Disease/*metabolism , Inflammation/*complications , Paratuberculosis/*complications, Alzheimer Disease/pathology ; Amyloidogenic Proteins/chemistry ; Amyloidogenic Proteins/metabolism ; Animals ; Autophagy ; Biomarkers ; Humans ; Mycobacterium avium subsp. paratuberculosis ; Mycobacterium bovis/immunology ; Paratuberculosis/immunology ; Paratuberculosis/microbiology |
| مستخلص: | This article prosecutes a case against the zoonotic pathogen Mycobacterium avium ss. paratuberculosis (MAP) as a precipitant of Alzheimer's disease (AD). Like the other major neurodegenerative diseases AD is, at its core, a proteinopathy. Aggregated extracellular amyloid protein plaques and intracellular tau protein tangles are the recognized protein pathologies of AD. Autophagy is the cellular housekeeping process that manages protein quality control and recycling, cellular metabolism, and pathogen elimination. Impaired autophagy and cerebral insulin resistance are invariant features of AD. With a backdrop of age-related low-grade inflammation (inflammaging) and heightened immune risk (immunosenescence), infection with MAP subverts glucose metabolism and further exhausts an already exhausted autophagic capacity. Increasingly, a variety of agents have been found to favorably impact AD; they are agents that promote autophagy and reduce insulin resistance. The potpourri of these therapeutic agents: mTOR inhibitors, SIRT1 activators and vaccines are seemingly random until one recognizes that all these agents also suppress intracellular mycobacterial infection. The zoonotic mycobacterial MAP causes a common fatal enteritis in ruminant animals. Humans are exposed to MAP from contaminated food products and from the environment. The enteritis in animals is called paratuberculosis or Johne's disease; in humans, it is the putative cause of Crohn's disease. Beyond Crohn's, MAP is associated with an increasing number of inflammatory and autoimmune diseases: sarcoidosis, Blau syndrome, autoimmune diabetes, autoimmune thyroiditis, multiple sclerosis, and rheumatoid arthritis. Moreover, MAP has been associated with Parkinson's disease. India is one county that has extensively studied the human bio-load of MAP; 30% of more than 28,000 tested individuals were found to harbor, or to have harbored, MAP. This article asserts an unfolding realization that MAP infection of humans 1) is widespread in its presence, 2) is wide-ranging in its zoonosis and 3) provides a plausible link connecting MAP to AD. Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Dow.) |
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| فهرسة مساهمة: | Keywords: Alzheimer’s disease; Crohn’s disease; Johne’s disease; MAP; Mycobacterium avium ss. paratuberculosis; autophagy; insulin resistance; rifampin |
| المشرفين على المادة: | 0 (Amyloidogenic Proteins) 0 (Biomarkers) |
| تواريخ الأحداث: | Date Created: 20210823 Date Completed: 20211220 Latest Revision: 20211220 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC8375433 |
| DOI: | 10.3389/fimmu.2021.714179 |
| PMID: | 34421917 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2021.714179 |