scholarly journals Recent Progress on Biological Activity of Amaryllidaceae and Further Isoquinoline Alkaloids in Connection with Alzheimer’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5240
Author(s):  
Lucie Cahlíková ◽  
Rudolf Vrabec ◽  
Filip Pidaný ◽  
Rozálie Peřinová ◽  
Negar Maafi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biological Activity ◽  
Life Expectancy ◽  
Neurodegenerative Disease ◽  
Elderly People ◽  
Recent Progress ◽  
Isoquinoline Alkaloids ◽  
Amaryllidaceae Alkaloids ◽  
Age Related

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease recognized as the most common form of dementia among elderly people. Due to the fact that the exact pathogenesis of AD still remains to be fully elucidated, the treatment is only symptomatic and available drugs are not able to modify AD progression. Considering the increase in life expectancy worldwide, AD rates are predicted to increase enormously, and thus the search for new AD drugs is urgently needed. Due to their complex nitrogen-containing structures, alkaloids are considered to be promising candidates for use in the treatment of AD. Since the introduction of galanthamine as an antidementia drug in 2001, Amaryllidaceae alkaloids (AAs) and further isoquinoline alkaloids (IAs) have been one of the most studied groups of alkaloids. In the last few years, several compounds of new structure types have been isolated and evaluated for their biological activity connected with AD. The present review aims to comprehensively summarize recent progress on AAs and IAs since 2010 up to June 2021 as potential drugs for the treatment of AD.

COMMENTARY: TREATING ALZHEIMER’S DISEASE : COMBINE OR FAIL ?

2019 ◽  
pp. 1-3
Author(s):  
S. Bakchine
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Neurodegenerative Disease ◽  
Elderly People

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease and accounts for more than 75% of cases of dementia in elderly people. Based on increasing life expectancy, it is predicted that the number of subjects suffering from AD and other dementias will reach the number of 131.5 millions worldwide in 2050 (1).

scholarly journals Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1572-1587 ◽  
Author(s):  
John D Arena ◽  
Douglas H Smith ◽  
Edward B Lee ◽  
Garrett S Gibbons ◽  
David J Irwin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Cell Types ◽  
Tau Pathology ◽  
Post Translational Modifications ◽  
Age Related ◽  
History Of ◽  
Severe Tbi

Abstract Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer’s disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer’s disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer’s disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer’s disease and ageing may rest solely on the pattern and distribution of pathology.

scholarly journals Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10619-10632 ◽  
Author(s):  
Faiz Ul Amin ◽  
Ali Kafash Hoshiar ◽  
Ton Duc Do ◽  
Yeongil Noh ◽  
Shahid Ali Shah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Nanoparticles ◽  
Neurodegenerative Disease ◽  
Amyloid Beta ◽  
Age Related ◽  
Electromagnetic Guidance ◽  
The Brain

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.

scholarly journals Overview of Alzheimer’s Disease and Some Therapeutic Approaches Targeting Aβby Using Several Synthetic and Herbal Compounds

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Sandeep Kumar Singh ◽  
Saurabh Srivastav ◽  
Amarish Kumar Yadav ◽  
Saripella Srikrishna ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Therapeutic Approaches ◽  
Age Related

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-βmetabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics.

scholarly journals Bridging Representation Gaps in Big Data: An Alzheimer's Disease Neuroimaging Initiative (ADNI) Investigation

2019 ◽  
Vol 34 (7) ◽  
pp. 1278-1278
Author(s):  
K Tureson ◽  
A I Gold ◽  
A D Thames
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Large Scale ◽  
Longitudinal Research ◽  
Disease Risk ◽  
Adult Population ◽  
Verbal Learning ◽  
Disease Assessment ◽  
Age Related

Abstract Objective Large-scale research consortium studies are increasingly used to help aid in early identification of age-related brain changes and neurodegenerative disease risk. Racial/ethnic minorities (REM) are severely underrepresented in publicly available datasets related to neurodegenerative disease. This is problematic given that the US older adult population will be comprised of 40% REM by 2050. As this population grows more diverse, it is crucial that Alzheimer’s disease (AD) risk factors are appropriately characterized and REM are represented in longitudinal research. The purpose of this study was to examine memory, Apolipoprotein E (APOE) status, and hippocampal volume (HV) data among REM participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Participants and Method We sampled 91 Latinx and Non-Hispanic Black (NHB) ADNI participants, which included 41 controls (CN; 39% Latinx) and 50 individuals with mild cognitive impairment (MCI; 52% Latinx). Measures included Logical Memory (LM) Delay, Rey Auditory Verbal Learning Test (RAVLT), Alzheimer’s Disease Assessment Cognitive 13-item Scale (ADAS13), APOE e4 and APOE e2 status, and HV. Groups did not differ by age, education, or memory performance. None of the Latinx sample were e2 carriers, whereas 32% of NHB were e2 carriers. Results For NHB and Latinx MCI groups, LM Delay scores positively predicted greater HV (NHB: R2 = .17, p = .04; Latinx: R2 = .16, p = .04). Better RAVLT performance predicted greater HV for the Latinx MCI group but not for the NHB MCI group (Latinx: R2 = .13, p = .06). For NHB CN, e4 status and ADAS13 were positively correlated (r = .59, p = .002) but negatively correlated for Latinx CN (r = -.58, p = .002). APOE e2 and RAVLT percent forgetting were negatively correlated for NHB MCI (r = -.49, p = .01). Conclusions There appears to be differential risk associated with heterozygous e4 status in Latinx and NHB. APOE e2 may have been protective in the context of e4 in NHB. The degree to which e2 is protective in Latinx is unknown. Results highlight the need for improved REM representation in large-scale studies to understand genetic risk and protective factors in REM.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

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