Cellular basis of Alzheimer′s disease

Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoë V.; Zurbriggen, Sebastian; Rajendran, Lawrence

doi:10.4103/0972-2327.74251

Cited by 15 publications

(13 citation statements)

References 39 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The disease can be characterized by massive cognitive decline, occurring in either sporadic or familial forms. Evidence suggests that abnormal production and accumulation of misfolded, toxic proteins like β-amyloid (Aβ) peptides, the microtubule-associated protein tau [ 2 ], and the presynaptic protein α-synuclein are involved in the pathogenesis of AD [ 3 ]. The pathological hallmarks of AD are the appearance of senile plaques and neurofibrillary tangles in the brain tissue, in addition to the development of cerebral amyloid angiopathy, with depositions of Aβ peptides in the vessel walls [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Changes in the Chemical Barrier Composition of Tears in Alzheimer’s Disease Reveal Potential Tear Diagnostic Biomarkers

et al. 2016

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, with increasing prevalence affecting millions of people worldwide. Currently, only autopsy is able to confirm the diagnosis with a 100% certainty, therefore, biomarkers from body fluids obtained by non-invasive means provide an attractive alternative for the diagnosis of Alzheimer`s disease. Global changes of the protein profile were examined by quantitative proteomics; firstly, electrophoresis and LC-MS/MS were used, thereafter, SRM-based targeted proteomics method was developed and applied to examine quantitative changes of tear proteins. Alterations in the tear flow rate, total tear protein concentration and composition of the chemical barrier specific to AD were demonstrated, and the combination of lipocalin-1, dermcidin, lysozyme-C and lacritin was shown to be a potential biomarker, with an 81% sensitivity and 77% specificity.

show abstract

Section: Introductionmentioning

confidence: 99%

Changes in the Chemical Barrier Composition of Tears in Alzheimer’s Disease Reveal Potential Tear Diagnostic Biomarkers

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This hyperphosphorylation of Tau is especially caused by the increased activity of kinases, namely glycogen synthase kinase-3 (GSK-3), CDK5, and the MAP/microtubule affinity-regulating kinase (MARK) which are activated by Aβ oligomers [ 2 , 28 , 30 , 31 , 32 ]. However, the inhibition of some phosphatases, including protein phosphatase 2A (PP2A) and calcineurin, also plays a crucial role, culminating in the formation of NFTs [ 28 , 30 , 33 , 34 , 35 ]. In general, significant evidence supports an Aβ-centered view of AD, and more research is still needed to understand if these two hypotheses are independent or inter-related paths.…”

Section: Alzheimer’s Disease Characterizationmentioning

confidence: 99%

New RNA-Based Breakthroughs in Alzheimer’s Disease Diagnosis and Therapeutics

2021

View full text Add to dashboard Cite

Dementia is described as the fifth leading cause of death worldwide and Alzheimer’s disease (AD) is recognized as the most common, causing a huge impact on health costs and quality of patients’ lives. The main hallmarks that are commonly associated with the pathologic process are amyloid deposition, pathologic Tau phosphorylation and neurodegeneration. It is still unclear how these events are linked to the disease progression, due to the complex pathologic mechanisms. Nevertheless, several hypotheses have been proposed for a better understanding of AD. The AD diagnosis is performed by using a combination of several tools to detect β-amyloid peptide (Aβ) deposits and modifications in cognitive performance, sometimes being expensive and invasive. In the treatment field, there is still an absence of effective treatments to delay or stop the progression of the disease, with most of the approved drugs used to relieve symptoms, and all of them with significant adverse side effects. Considering all limitations, the need to establish new and more effective diagnostic and therapeutic strategies becomes clear. This review aims not only to describe the disease and its impact but also to collect the currently available diagnostic and therapeutic strategies, highlighting new promising RNA-based strategies for AD.

show abstract

“…These two sites are near the extracellular side of APP's transmembrane domain, allowing for more efficient cleavage. α-and β-secretase proteases compete for APP cleavage to give two products: a soluble APP and a membrane-anchored C-terminal stub [20,[25][26][27][28][29]. This stub is the site of the crucial AD indicated cleavage, where γ-secretase acts.…”

Section: Beta-amyloid Proteinmentioning

confidence: 99%

“…This stub is the site of the crucial AD indicated cleavage, where γ-secretase acts. "While the division of C83 generates the 6-κDa APP intracellular domain (AICD) and releases the N-terminal 3κDa peptide (p3) into the extracellular space, cleavage of C99 generates AICD and the Aβ peptide," [20]. The processing of APP by beta-secretase and gamma-secretase and the corresponding formation of beta-amyloid protein is known as the amyloidogenic pathway.…”

Section: Beta-amyloid Proteinmentioning

confidence: 99%

Investigating TRSV Phytoalexin Infusions as a Novel Treatment for Alzheimer’s Disease Using ApoE4 Plasmid Transfections in Neuro2a Cell Complexes

Gandhi

2020

Preprint

View full text Add to dashboard Cite

Because the accumulation of amyloid plaques plays a central role in the pathogenesis of Alzheimer's disease (AD) and is responsible for many of its neurodegenerative effects, this project aims to evaluate the effectiveness of TRSV phytoalexin infusions as a novel treatment for the disease by comparing three separate agents and determining its impact on the accumulation of amyloid plaques in mouse Neuro2a cells. The experimental model is as follows: Neuro2a cells were first thawed using incubation and centrifugation techniques. The subculturing protocol was then performed to maximize cellular viability using DPBS and TrypLE dissociation reagents. The cells were transfected with pCMV4-ApoE4 bacterial plasmid using Opti-MEM medium and Lipofectamine LTX while also being treated with phytoalexin agents. Bradford's assay was performed on the samples using CBB G-250 reagent, and they were run through a spectrophotometer and a Python low-pass filter to generate readings. The experimental data showed that natural grape seed phytoalexin extract was the most effective treating agent, followed by curcumin extract and synthetic RDS phytoalexin. All treating agents lessened the accumulation of the amyloid plaques significantly, supporting the novel infusion protocol as a treatment for AD.

show abstract

Cellular basis of Alzheimer′s disease

Cited by 15 publications

References 39 publications

Changes in the Chemical Barrier Composition of Tears in Alzheimer’s Disease Reveal Potential Tear Diagnostic Biomarkers

Changes in the Chemical Barrier Composition of Tears in Alzheimer’s Disease Reveal Potential Tear Diagnostic Biomarkers

New RNA-Based Breakthroughs in Alzheimer’s Disease Diagnosis and Therapeutics

Investigating TRSV Phytoalexin Infusions as a Novel Treatment for Alzheimer’s Disease Using ApoE4 Plasmid Transfections in Neuro2a Cell Complexes

Contact Info

Product

Resources

About