Interleukin-17A in Alzheimer’s disease: recent advances and controversies

: Alzheimer’s disease (AD) is a progressive neurodegenerative disease which mainly affects older adults. Although the global burden of AD is increasing year by year, the causes of AD remain largely unknown. Numerous basic and clinical studies have shown that interleukin-17A (IL-17A) may play a significant role in the pathogenesis of AD. A comprehensive assessment ofthe role of IL-17A in AD would benefit the diagnosis, understanding of etiology and treatment. However, over the past decade controversies remain regarding the expression level and role of IL-17A in AD. We have incorporated newly published researches and point out that IL-17A expression levels may vary along with the development of AD, exercising different roles at different stages of AD, although much more work remains to be done to support the potential role of IL-17A in AD-related pathology.Here, it is our intention to review the underlying mechanisms of IL-17A in AD and address the current controversies, in an effort to clarify the results of existing research and suggest future studies.

Download Full-text

Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22694 ◽

2021 ◽

Author(s):

Tauqeerunnisa Syeda ◽

Jason R. Cannon

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potential Role ◽

Environmental Exposures

Download Full-text

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

Download Full-text

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.

Download Full-text

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.

Download Full-text

Physical Activity in the Prevention of Alzheimer's Disease

Kinesiology Review ◽

10.1123/kr.2014-0075 ◽

2015 ◽

Vol 4 (1) ◽

pp. 28-38 ◽

Cited By ~ 2

Author(s):

Jennifer L. Etnier

Keyword(s):

Physical Activity ◽

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitively Impaired ◽

Future Directions ◽

Positive Effects ◽

Additional Funding ◽

Promising Area

Alzheimer's disease is a chronic illness characterized by clinical cognitive impairment. A behavioral strategy that is being explored in the prevention of Alzheimer's disease is physical activity. Evidence from randomized controlled trials (RCTs) testing the effects of physical activity for cognitively normal older adults supports that physical activity benefits cognitive performance. Evidence from prospective studies supports a protective effect of physical activity with reductions in the risk of cognitive decline ranging from 28% to 45%. RCTs with cognitively impaired older adults also generally support positive effects with greater benefits evident for aerobic interventions. Research examining the potential moderating role of apolipoprotein E (APOE) has yielded mixed results, but the majority of the studies support that physical activity most benefits those who are at greatest genetic risk of Alzheimer's disease. Future directions for research are considered with an emphasis on the need for additional funding to support this promising area of research.

Download Full-text