The potential role of microRNA-146 in Alzheimer’s disease: Biomarker or therapeutic target?

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

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The potential role of non-steroidal anti-inflammatory drugs in treating Alzheimer’s disease

Expert Opinion on Investigational Drugs ◽

10.1517/13543784.13.11.1469 ◽

2004 ◽

Vol 13 (11) ◽

pp. 1469-1481 ◽

Cited By ~ 31

Author(s):

Bruno P Imbimbo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potential Role ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Towards a Consensus on Alzheimer’s Disease Comorbidity?

Journal of Clinical Medicine ◽

10.3390/jcm10194360 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4360

Author(s):

Iska Avitan ◽

Yudit Halperin ◽

Trishna Saha ◽

Naamah Bloch ◽

Dana Atrahimovich ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potential Role ◽

Oxygen Species ◽

Degenerative Diseases ◽

Comorbid Diseases

Alzheimer’s disease (AD) is often comorbid with other pathologies. First, we review shortly the diseases most associated with AD in the clinic. Then we query PubMed citations for the co-occurrence of AD with other diseases, using a list of 400 common pathologies. Significantly, AD is found to be associated with schizophrenia and psychosis, sleep insomnia and apnea, type 2 diabetes, atherosclerosis, hypertension, cardiovascular diseases, obesity, fibrillation, osteoporosis, arthritis, glaucoma, metabolic syndrome, pain, herpes, HIV, alcoholism, heart failure, migraine, pneumonia, dyslipidemia, COPD and asthma, hearing loss, and tobacco smoking. Trivially, AD is also found to be associated with several neurodegenerative diseases, which are disregarded. Notably, our predicted results are consistent with the previously published clinical data and correlate nicely with individual publications. Our results emphasize risk factors and promulgate diseases often associated with AD. Interestingly, the comorbid diseases are often degenerative diseases exacerbated by reactive oxygen species, thus underlining the potential role of antioxidants in the treatment of AD and comorbid diseases.

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Potential Role of Phosphoglycerol Dihydroceramide Produced by Periodontal Pathogen Porphyromonas gingivalis in the Pathogenesis of Alzheimer’s Disease

Frontiers in Immunology ◽

10.3389/fimmu.2020.591571 ◽

2020 ◽

Vol 11 ◽

Author(s):

Chiaki Yamada ◽

Juliet Akkaoui ◽

Anny Ho ◽

Carolina Duarte ◽

Richard Deth ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Porphyromonas Gingivalis ◽

Virulence Factors ◽

Potential Role ◽

Sirtuin 1 ◽

Periodontal Pathogen ◽

Secretory Phenotype ◽

Aβ42 Peptide

BackgroundAmong different types of sphingolipids produced by human cells, the possible engagement of ceramide species in the pathogenesis of Alzheimer’s disease (AD) has attracted recent attention. While ceramides are primarily generated by de novo synthesis in mammalian cells, only a limited number of bacterial species, produce ceramides, including phosphoglycerol dihydroceramide (PGDHC) that is produced by the key periodontal pathogen Porphyromonas gingivalis. Emerging evidence indicates that virulence factors produced by P. gingivalis, such as lipopolysaccharide and gingipain, may be engaged in the initiation and/or progression of AD. However, the potential role of PGDHC in the pathogenesis of AD remains unknown. Therefore, the aim of this study was to evaluate the influence of PGDHC on hallmark findings in AD.Material and MethodsCHO-7WD10 and SH-SY-5Y cells were exposed to PGDHC and lipopolysaccharide (LPS) isolated from P. gingivalis. Soluble Aβ42 peptide, amyloid precursor protein (APP), phosphorylated tau and senescence-associated secretory phenotype (SASP) factors were quantified using ELISA and Western blot assays. ResultsOur results indicate that P. gingivalis (Pg)-derived PGDHC, but not Pg-LPS, upregulated secretion of soluble Aβ42 peptide and expression of APP in CHO-7WD10 cells. Furthermore, hyperphosphorylation of tau protein was observed in SH-SY-5Y cells in response to PGDHC lipid. In contrast, Pg-LPS had little, or no significant effect on the tau phosphorylation induced in SH-SY-5Y cells. However, both PGDHC and Pg-LPS contributed to the senescence of SH-SY5Y cells as indicated by the production of senescence-associated secretory phenotype (SASP) markers, including beta-galactosidase, cathepsin B (CtsB), and pro-inflammatory cytokines TNF-α, and IL-6. Additionally, PGDHC diminished expression of the senescence-protection marker sirtuin-1 in SH-SY-5Y cells.ConclusionsAltogether, our results indicate that P. gingivalis-derived PGDHC ceramide promotes amyloidogenesis and hyperphosphorylation, as well as the production of SASP factors. Thus, PGDHC may represent a novel class of bacterial-derived virulence factors for AD associated with periodontitis.

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