Licensed Anti-Microbial Drugs Logical for Clinical Trials against Pathogens Currently Suspected in Alzheimer’s Disease

Norins, Leslie C.

doi:10.3390/antibiotics10030327

Cited by 7 publications

(3 citation statements)

References 53 publications

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“…274 Unfortunately, there is no epidemiological data for antibiotics lifelong use and AD development like it exists for antivirals or for nonsteroidal anti-inflammatory drugs (NSAIDs). This would be worthwhile to perform 275 but keeping in mind that a possible antimicrobial resistance may develop.…”

Section: Prevention/treatment Of Infectionsmentioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

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Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.

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Section: Prevention/treatment Of Infectionsmentioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

View full text Add to dashboard Cite

show abstract

“…Increasing epidemiologic and experimental data suggest a role for chronic bacterial and viral infections as risk factors for neurodegenerative diseases [82][83][84]. HERVs have repeatedly been implicated in brain disorders [85][86][87] and while this article will primarily discuss the age-related neurodegenerative diseases, it is worth noting the recognition of HERV in the etiopathology of schizophrenia [88,89].…”

Section: Neurodegenerationmentioning

confidence: 99%

<em>Mycobacterium paratuberculosis</em>: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?

Dow,

Pierce,

Sechi

2024

Preprint

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Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the devel-opment of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granu-lomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

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“…Although no specific agent has been identified as a cause of AD, a number of infectious agents have been linked to AD [84,109,110]. This association is bolstered by the knowledge that AD's primary pathologic protein, amyloid, is an antimicrobial peptide [111,112].…”

Section: Ad and Mapmentioning

confidence: 99%

<em>Mycobacterium paratuberculosis</em>: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?

Dow,

Pierce,

Sechi

2024

Preprint

View full text Add to dashboard Cite

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

show abstract

Licensed Anti-Microbial Drugs Logical for Clinical Trials against Pathogens Currently Suspected in Alzheimer’s Disease

Cited by 7 publications

References 53 publications

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

<em>Mycobacterium paratuberculosis</em>: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?

<em>Mycobacterium paratuberculosis</em>: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer?

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