Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of patients with dementia, including Alzheimer's disease (AD), is growing. The disease was first diagnosed and described at the beginning of the 20th century. However, to this day, there is no effective causal therapy, and symptomatic treatment often improves patients' quality of life only for a short time. The current pharmacological therapies are based mainly on the oldest hypotheses of the disease-cholinergic (drugs affecting the cholinergic system are available), the hypothesis of amyloid-β aggregation (an anti-amyloid drug was conditionally approved by the FDA in 2020), and one drug is an N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine). Hypotheses about AD pathogenesis focus on the nervous system and the brain. As research progresses, it has become known that AD can be caused by diseases that have been experienced over the course of a lifetime, which could also affect other organs. In this review, we focus on the potential association of AD with the digestive system, primarily the gut microbiota. The role of diet quality in preventing and alleviating Alzheimer's disease is also discussed. The problem of neuroinflammation, which may be the result of microbiota disorders, is also described. An important aspect of the work is the chapter on the treatment strategies for changing the microbiota, potentially protecting against the disease and alleviating its course in the initial stages.
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http://dx.doi.org/10.3390/ijms23094862 | DOI Listing |
Adv Sci (Weinh)
January 2025
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology.
View Article and Find Full Text PDFActa Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFNeurotherapeutics
January 2025
Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. Electronic address:
Amyloidogenic protein aggregation is a pathological hallmark of Alzheimer's Disease (AD). As such, this critical feature of the disease has been instrumental in guiding research on the mechanistic basis of disease, diagnostic biomarkers and preventative and therapeutic treatments. Here we review identified molecular triggers and modulators of aggregation for two of the proteins associated with AD: amyloid beta and tau.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
First Operating Room, The First Hospital of Jilin University, Changchun, China. Electronic address:
Background: Certain peripheral proteins are believed to be involved in the development of Alzheimer's disease (AD), but the roles of other new protein biomarkers are still unclear. Current treatments aim to manage symptoms, but they are not effective in stopping the progression of the disease. New drug targets are needed to prevent Alzheimer's disease.
View Article and Find Full Text PDFNeuroscience
January 2025
Departamento de Genómica, Instituto de Investigaciones Biológicas Clemente Estable, MEC, Av. Italia 3318, Montevideo, CP 11600, Uruguay; Departamento de Biología Celular y Molecular, Facultad de Ciencias, Universidad de la República, Iguá, Montevideo, 4225, CP 11400, Uruguay. Electronic address:
Local protein synthesis (LPS) in axons is now recognized as a physiological process, participating both in the maintenance of axonal function and diverse plastic phenomena. In the last decades of the 20th century, the existence and function of axonal LPS were topics of significant debate. Very early, axonal LPS was thought not to occur at all and was later accepted to play roles only during development or in response to specific conditions.
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