From Infection to Inoculation: Expanding the Microbial Hypothesis of
Alzheimer’s Disease

Dorszewska, Jolanta; Hurła, Mikołaj; Banaszek, Natalia; Kobylarek, Domink; Piekut, Thomas; Kozubski, Wojciech

doi:10.2174/1567205020666230202155404

Cited by 5 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Myriad theories have been forwarded to explain AD pathogenesis, ranging from those implicating an infectious etiology [112,113] to others suggesting that it is ultimately a metabolic disorder deserving of the name 'type 3 diabetes' [114,115]. Here, however, we focus on the already highly substantiated oxidation-inflammation thesis, which postulates that AD pathology predominantly arises from an imbalance between antioxidant activity and oxidative stress that derives from and exacerbates inflammatory responses [116,117].…”

Section: Alzheimer's Diseasementioning

confidence: 98%

Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases

Korczowska-Łącka,

Słowikowski,

Piekut

et al. 2023

Antioxidants

Self Cite

View full text Add to dashboard Cite

In diseases of the central nervous system, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and even epilepsy and migraine, oxidative stress load commonly surpasses endogenous antioxidative capacity. While oxidative processes have been robustly implicated in the pathogenesis of these diseases, the significance of particular antioxidants, both endogenous and especially exogenous, in maintaining redox homeostasis requires further research. Among endogenous antioxidants, enzymes such as catalase, superoxide dismutase, and glutathione peroxidase are central to disabling free radicals, thereby preventing oxidative damage to cellular lipids, proteins, and nucleic acids. Whether supplementation with endogenously occurring antioxidant compounds such as melatonin and glutathione carries any benefit, however, remains equivocal. Similarly, while the health benefits of certain exogenous antioxidants, including ascorbic acid (vitamin C), carotenoids, polyphenols, sulforaphanes, and anthocyanins are commonly touted, their clinical efficacy and effectiveness in particular neurological disease contexts need to be more robustly defined. Here, we review the current literature on the cellular mechanisms mitigating oxidative stress and comment on the possible benefit of the most common exogenous antioxidants in diseases such as AD, PD, ALS, HD, stroke, epilepsy, and migraine. We selected common neurological diseases of a basically neurodegenerative nature.

show abstract

Section: Alzheimer's Diseasementioning

confidence: 98%

Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases

Korczowska-Łącka,

Słowikowski,

Piekut

et al. 2023

Antioxidants

Self Cite

View full text Add to dashboard Cite

show abstract

“…Natural bacteria living in the GI are involved in the modulation of immune responses and digestive processes, such as carbohydrate fermentation and vitamin synthesis [66]. On the other hand, intestinal dysbiosis could contribute to different stages of AD pathogenesis through the secretion of neuroactive molecules [67][68][69][70] and harmful metabolites, such as lipopolysaccharide (LPS). LPS is a bacterial endotoxin that triggers the release of pro-inflammatory cytokines and superoxide [71,72].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

MicroRNAs and MAPKs: Evidence of These Molecular Interactions in Alzheimer’s Disease

Raffaele

Silvestro

Mazzon

2023

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disorder known to be the leading cause of dementia worldwide. Many microRNAs (miRNAs) were found deregulated in the brain or blood of AD patients, suggesting a possible key role in different stages of neurodegeneration. In particular, mitogen-activated protein kinases (MAPK) signaling can be impaired by miRNA dysregulation during AD. Indeed, the aberrant MAPK pathway may facilitate the development of amyloid-beta (Aβ) and Tau pathology, oxidative stress, neuroinflammation, and brain cell death. The aim of this review was to describe the molecular interactions between miRNAs and MAPKs during AD pathogenesis by selecting evidence from experimental AD models. Publications ranging from 2010 to 2023 were considered, based on PubMed and Web of Science databases. According to obtained data, several miRNA deregulations may regulate MAPK signaling in different stages of AD and conversely. Moreover, overexpressing or silencing miRNAs involved in MAPK regulation was seen to improve cognitive deficits in AD animal models. In particular, miR-132 is of particular interest due to its neuroprotective functions by inhibiting Aβ and Tau depositions, as well as oxidative stress, through ERK/MAPK1 signaling modulation. However, further investigations are required to confirm and implement these promising results.

show abstract

“…Scientific research into whether microorganisms can cause neurodegeneration goes back over 30 years. Many theories have been put forward as to how microorganisms can lead to the development of neurodegeneration, ranging from their ability to interfere with protein trafficking and cause protein aggregation, the activation of microglia toward a pro-inflammatory phenotype consistent with poorer clearance of cellular debris, and a number of other processes (Piekut et al, 2022 ; Dorszewska et al, 2023 ).…”

mentioning

confidence: 99%

“…The number of people over 60 is increasing worldwide. According to modern knowledge, the aging process contributes to a decrease in the efficiency of defense and repair systems and leads to subclinical changes in the central nervous system, including morphological and functional deterioration of brain function, progressive loss of neurons, reduced levels of neurotransmitters, excessive inflammation, impaired integrity vascular, neuroplasticity disorders, the influence of infectious agents, and increase in pathological proteins (Marchetti and Marie, 2011;Dorszewska, 2013;Dorszewska et al, 2016Dorszewska et al, , 2020Dorszewska et al, , 2023Kozubski et al, 2021;Piekut et al, 2022) (Figure 1).…”

mentioning

confidence: 99%