scholarly journals Kinin B2 Receptor Activation Prevents the Evolution of Alzheimer’s Disease Pathological Characteristics in a Transgenic Mouse Model

2020 ◽  
Vol 13 (10) ◽  
pp. 288
Author(s):  
Marielza Andrade Nunes ◽  
Mariana Toricelli ◽  
Natalia Mendes Schöwe ◽  
Helena Nascimento Malerba ◽  
Karis Ester Dong-Creste ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Functional Disability ◽  
Therapeutic Option ◽  
Receptor Activation ◽  
Hippocampal Culture ◽  
Kinin System ◽  
Organotypic Hippocampal Culture ◽  
Kallikrein Kinin System

Background: Alzheimer’s disease is mainly characterized by remarkable neurodegeneration in brain areas related to memory formation. This progressive neurodegeneration causes cognitive impairment, changes in behavior, functional disability, and even death. Our group has demonstrated changes in the kallikrein–kinin system (KKS) in Alzheimer’s disease (AD) experimental models, but there is a lack of evidence about the role of the KKS in Alzheimer’s disease. Aim: In order to answer this question, we evaluated the potential of the kinin B2 receptors (BKB2R) to modify AD characteristics, particularly memory impairment, neurodegeneration, and Aβ peptide deposition. Methods: To assess the effects of B2, we used transgenic Alzheimer’s disease mice treated with B2 receptor (B2R) agonists and antagonists, and performed behavioral and biochemical tests. In addition, we performed organotypic hippocampal culture of wild-type (WT) and transgenic (TG) animals, where the density of cytokines, neurotrophin BDNF, activated astrocyte marker S100B, and cell death were analyzed after treatments. Results: Treatment with the B2R agonist preserved the spatial memory of transgenic mice and decreased amyloid plaque deposition. In organotypic hippocampal culture, treatment with B2R agonist decreased cell death, neuroinflammation, and S100B levels, and increased BDNF release. Conclusions: Our results indicate that the kallikrein–kinin system plays a beneficial role in Alzheimer’s disease through B2R activation. The use of B2R agonists could, therefore, be a possible therapeutic option for patients diagnosed with Alzheimer’s disease.

scholarly journals Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates

2021 ◽  
Vol 7 (13) ◽  
pp. eabf9180
Author(s):  
A. Duro-Castano ◽  
C. Borrás ◽  
V. Herranz-Pérez ◽  
M. C. Blanco-Gandía ◽  
I. Conejos-Sánchez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neurons ◽  
Brain Distribution ◽  
Olfactory Memory ◽  
Hippocampal Culture ◽  
Amyloid Aggregate ◽  
Organotypic Hippocampal Culture ◽  
Β Amyloid ◽  
Prevalent Form

Alzheimer’s disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic β amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment.

Is it All Said for NSAIDs in Alzheimer’s Disease? Role of Mitochondrial Calcium Uptake

2018 ◽  
Vol 15 (6) ◽  
pp. 504-510 ◽  
Author(s):  
Sara Sanz-Blasco ◽  
Maria Calvo-Rodríguez ◽  
Erica Caballero ◽  
Monica Garcia-Durillo ◽  
Lucia Nunez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Amyloid Β ◽  
Epidemiological Data ◽  
Amyloid Β Peptide ◽  
Aβ Oligomers ◽  
Mitochondrial Potential ◽  
Disease Modifying Drugs ◽  
Definitive Evidence

Objectives: Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing. Possible explanations include the view that NSAIDs and other possible disease-modifying drugs should be provided before the patients develop symptoms of AD or cognitive decline. In addition, NSAID targets for neuroprotection are unclear. Both COX-dependent and independent mechanisms have been proposed, including γ-secretase that cleaves the amyloid precursor protein (APP) and yields amyloid β peptide (Aβ). Methods: We have proposed a neuroprotection mechanism for NSAIDs based on inhibition of mitochondrial Ca2+ overload. Aβ oligomers promote Ca2+ influx and mitochondrial Ca2+ overload leading to neuron cell death. Several non-specific NSAIDs including ibuprofen, sulindac, indomethacin and Rflurbiprofen depolarize mitochondria in the low µM range and prevent mitochondrial Ca2+ overload induced by Aβ oligomers and/or N-methyl-D-aspartate (NMDA). However, at larger concentrations, NSAIDs may collapse mitochondrial potential (ΔΨ) leading to cell death. Results: Accordingly, this mechanism may explain neuroprotection at low concentrations and damage at larger doses, thus providing clues on the failure of promising trials. Perhaps lower NSAID concentrations and/or alternative compounds with larger dynamic ranges should be considered for future trials to provide definitive evidence of neuroprotection against AD.

Predicting Alzheimer's Disease Progression by Combining Multiple Measures

2021 ◽  
Author(s):  
Nour Zawawi ◽  
Heba Gamal Saber ◽  
Mohamed Hashem ◽  
Tarek F.Gharib
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Early Diagnosis ◽  
Nerve Cell ◽  
Neurological Examination ◽  
Medical Data ◽  
Complex Interactions ◽  
Dementia Patients ◽  
Nerve Cell Death

Alzheimer's disease (AD) is a degenerative brain ailment that affects millions worldwide. It is the most common form of dementia. Patients with an early diagnosis of Alzheimer's disease have a strong chance of preventing additional brain damage by halting nerve cell death. At the same time, it begins to progress several years before any symptoms appear. The variety of data is the biggest problem encountered during diagnosis. Neurological examination, brain imaging, and often asked questions from his connected closed relatives are the three forms of data that a neurologist or geriatrics employs to diagnose patients. One of the biggest questions which need answering is the choice of a convenient feature. The main objective of this paper is to help neurologists or geriatricians diagnose patient conditions. It proposes a new hybrid model for features extracted from medical data. It discusses AD's early diagnosis and progression for all features considered in the diagnosis and their complex interactions. It proves to have the best accuracy when compared with the state-ofthe-art algorithm. Also, it proves to be more accurate against some recent research ideas. It got 95% in all cases, considering this work focused more on increasing the number of instances in comparison.

Theracurmin supplementation may be a therapeutic option for older patients with alzheimer’s disease: a 6-month retrospective follow-up study

2021 ◽  
Vol 19 ◽  
Author(s):  
Fatma Sena Dost ◽  
Derya Kaya ◽  
Mehmet Selman Ontan ◽  
Neziha Erken ◽  
Esra Ateş Bulut ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Patients ◽  
Therapeutic Option ◽  
Disease Course ◽  
Clock Drawing Test ◽  
Global Challenge ◽  
Follow Up Study ◽  
Therapeutic Opportunity

Background: Alzheimer’s Disease (AD) is still a great global challenge and agents with various mechanisms represent a promising therapeutic opportunity. Theracurmin, a very highly absorbable curcumin formulation, was shown to improve memory and attention in non-demented people. Objective: To investigate the effect of Theracurmin on disease course in elderly patients with mild cognitive impairment (MCI) and AD. Methods: This follow-up study was performed retrospectively on 93 patients with MCI or AD. All patients underwent comprehensive geriatric assessment, including Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), clock-drawing test, activities of daily living (ADL), at baseline and end of the 6th-month. 19 patients with AD and 17 with MCI were treated with Theracurmin 180 mg/day per oral. Results: MMSE, MOCA and instrumental ADL scores decreased in AD patients that were not treated with Theracurmin (p<0.001, p=0.011, and p=0.004, respectively), whereas these scores remained stable in those treated with Theracurmin. This stabilization in the instrumental ADL was also observed in MCI patients treated with Theracurmin. During the follow-up, three of MCI patients who did not receive Theracurmin progressed to AD, whereas only one patient progressed in those who received it. Conclusion: Theracurmin seems to be a therapeutic option for elderly patients with AD and MCI via providing stabilization of the disease course by preventing progressive loss in cognitive functions and ADLs.

P3-053: (-)-PHENSERINE (PHEN) AND THE PREVENTION OF PRE-PROGRAMMED CELL DEATH IN ALZHEIMER'S DISEASE (AD) AND MILD TRAUMATIC BRAIN INJURY (MTBI)

2006 ◽  
Vol 14 (7S_Part_20) ◽  
pp. P1083-P1083
Author(s):  
Daniela Lecca ◽  
Miaad Bader ◽  
David Tweedie ◽  
Debomoy K. Lahiri ◽  
Robert E. Becker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Cell Death ◽  
Brain Injury ◽  
Programmed Cell Death ◽  
Mild Traumatic Brain Injury
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