Mitochondrial calcium uniporter as a potential therapeutic strategy for Alzheimer’s disease

2019 ◽  
Vol 32 (2) ◽  
pp. 65-71 ◽  
Author(s):  
Anila Venugopal ◽  
Mahalaxmi Iyer ◽  
Venkatesh Balasubramanian ◽  
Balachandar Vellingiri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Calcium Homeostasis ◽  
Therapeutic Strategy ◽  
Neurodegenerative Disorder ◽  
Amyloid Plaque ◽  
Mitochondrial Calcium ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter

AbstractAlzheimer’s disease (AD), a neurodegenerative disorder, is the leading cause of dementia in the world whose aetiology is still unclear. AD was always related to ageing though there have been instances where people at an early age also succumb to this disease. With medical advancements, the mortality rate has significantly reduced which also makes people more prone to AD. AD is rare, yet the prominent disease has been widely studied with several hypotheses trying to understand the workings of its onset. The most recent and popular hypothesis in AD is the involvement of mitochondrial dysfunction and calcium homeostasis in the development of the disease though their exact roles are not known. With the sudden advent of the mitochondrial calcium uniporter (MCU), many previously known pathological hallmarks of AD may be better understood. Several studies have shown the effect of excess calcium in mitochondria and the influence of MCU complex in mitochondrial function. In this article, we discuss the possible involvement of MCU in AD by linking the uniporter to mitochondrial dysfunction, calcium homeostasis, reactive oxygen species, neurotransmitters and the hallmarks of AD – amyloid plaque formation and tau tangle formation.

scholarly journals Mitochondrial calcium uniporter complex activation protects against calcium alternans in atrial myocytes

2020 ◽  
Vol 319 (4) ◽  
pp. H873-H881
Author(s):  
Yuriana Oropeza-Almazán ◽  
Lothar A. Blatter
Keyword(s):  
Cardiac Arrhythmia ◽  
Therapeutic Strategy ◽  
Conclusive Evidence ◽  
Mitochondrial Calcium ◽  
Atrial Myocytes ◽  
Uptake Inhibition ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter ◽  
Ca Uptake ◽  
Arrhythmia Prevention

This study provides conclusive evidence that mitochondrial Ca uptake and retention protects from Ca alternans, whereas uptake inhibition enhances Ca alternans. The data suggest pharmacological mitochondrial Ca cycling modulation as a potential therapeutic strategy for alternans-related cardiac arrhythmia prevention.

Mitochondrial calcium uniporter blocker prevents cardiac mitochondrial dysfunction induced by iron overload in thalassemic mice

BioMetals ◽  
2012 ◽  
Vol 25 (6) ◽  
pp. 1167-1175 ◽  
Author(s):  
Sirinart Kumfu ◽  
Siriporn Chattipakorn ◽  
Suthat Fucharoen ◽  
Nipon Chattipakorn
Keyword(s):  
Iron Overload ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Calcium ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter

scholarly journals BLOCKING MITOCHONDRIAL CALCIUM UNIPORTER COMPLETELY PREVENTS CARDIAC MITOCHONDRIAL DYSFUNCTION CAUSED BY IRON OVERLOAD

2013 ◽  
Vol 61 (10) ◽  
pp. E705 ◽  
Author(s):  
Jirapas Sripetchwandee ◽  
Samuel Kenknight ◽  
Jantira Sanit ◽  
Siriporn Chattipakorn ◽  
Nipon Chattipakorn
Keyword(s):  
Iron Overload ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Calcium ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter

scholarly journals Altered Blood Levels of Anti-Gal Antibodies in Alzheimer’s Disease: A New Clue to Pathogenesis?

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 538
Author(s):  
Antonella Angiolillo ◽  
Alessandro Gandaglia ◽  
Alessia Arcaro ◽  
Andrea Carpi ◽  
Fabrizio Gentile ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Plaque ◽  
Amyloid Peptide ◽  
Blood Levels ◽  
Potential Link ◽  
Altered Blood ◽  
New Biomarkers ◽  
First Time

Alzheimer’s disease is a neurodegenerative disorder whose pathological mechanisms, despite recent advances, are not fully understood. However, the deposition of beta amyloid -peptide and neuroinflammation, which is probably aggravated by dysbiotic microbiota, seem to play a key role. Anti-Gal are the most abundant xenoreactive natural antibodies. They are supposed to stem from immunization against the gut microbiota and have been implicated in the pathogenesis of several diseases, including multiple sclerosis. These antibodies target the alpha-Gal epitope, expressed on the terminal sugar units of glycoprotein or glycolipid of all mammals except apes, Old World monkeys and humans. The alpha-Gal is constitutively expressed in several bacteria constituting the brain microbiota, and alpha-Gal-like epitopes have been detected in gray matter, amyloid plaque, neurofibrillary tangles and corpora amylacea of the human brain, suggesting a potential link between anti-Gal and Alzheimer’s disease etiopathogenesis. For the first time, our study searched for possible alterations of anti-Gal immunoglobulin levels in Alzheimer’s disease patients. IgG and IgM blood levels were significantly lower, and IgA significantly higher in patients than in healthy subjects. These results suggest that such immunoglobulins might be implicated in Alzheimer’s disease pathogenesis and open new scenarios in the research for new biomarkers and therapeutic strategies.

scholarly journals Early candidate urine biomarkers for detecting Alzheimer’s disease before beta amyloid plaque deposition in an APP (swe)/PSEN1dE9transgenic mouse model

2018 ◽  
Author(s):  
Fanshuang Zhang ◽  
Jing Wei ◽  
Xundou Li ◽  
Chao Ma ◽  
Youhe Gao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Neurodegenerative Disorder ◽  
Amyloid Plaque ◽  
Beta Amyloid ◽  
Plaque Deposition ◽  
Urine Biomarkers ◽  
Old Mice

AbstractAlzheimer’s disease (AD) is an incurable age-associated neurodegenerative disorder that is characterized by irreversible progressive cognitive deficits and extensive brain damage. The identification of candidate biomarkers before beta amyloid plaque deposition occurs is therefore of great importance for the early intervention of AD. Urine, which is not regulated by homeostatic mechanisms, theoretically accumulates changes associated with AD earlier than cerebrospinal fluid and blood. In this study, an APP (swe)/PSEN1dE9 transgenic mouse model was used to identify candidate biomarkers for early AD. Urine samples were collected from 4-, 6-, and 8-month-old transgenic mouse models, and the urinary proteomes were profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The levels of 33 proteins differed significantly between wild-type and 4-month-old mice, which had not started to deposit beta amyloid plaque. Among these proteins, 16 have been associated with the mechanisms of AD, while 9 have been suggested as AD biomarkers. Our results indicated that urine proteins enable detecting AD before beta amyloid plaque deposition, which may present an opportunity for intervention.

scholarly journals Intracellular Calcium Dysregulation: Implications for Alzheimer’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Simona Magi ◽  
Pasqualina Castaldo ◽  
Maria Loredana Macrì ◽  
Marta Maiolino ◽  
Alessandra Matteucci ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intracellular Calcium ◽  
Calcium Homeostasis ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Calcium Stores ◽  
Cellular Mechanisms ◽  
Calcium Dysregulation ◽  
Review Reports

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by progressive neuronal loss. AD is associated with aberrant processing of the amyloid precursor protein, which leads to the deposition of amyloid-βplaques within the brain. Together with plaques deposition, the hyperphosphorylation of the microtubules associated protein tau and the formation of intraneuronal neurofibrillary tangles are a typical neuropathological feature in AD brains. Cellular dysfunctions involving specific subcellular compartments, such as mitochondria and endoplasmic reticulum (ER), are emerging as crucial players in the pathogenesis of AD, as well as increased oxidative stress and dysregulation of calcium homeostasis. Specifically, dysregulation of intracellular calcium homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Aberrant calcium signaling has been considered a phenomenon mainly related to the dysfunction of intracellular calcium stores, which can occur in both neuronal and nonneuronal cells. This review reports the most recent findings on cellular mechanisms involved in the pathogenesis of AD, with main focus on the control of calcium homeostasis at both cytosolic and mitochondrial level.

Mitochondrial calcium uniporter blocker effectively prevents brain mitochondrial dysfunction caused by iron overload

Life Sciences ◽  
2013 ◽  
Vol 92 (4-5) ◽  
pp. 298-304 ◽  
Author(s):  
Jirapas Sripetchwandee ◽  
Jantira Sanit ◽  
Nipon Chattipakorn ◽  
Siriporn C. Chattipakorn
Keyword(s):  
Iron Overload ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Calcium ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter

Tau in Alzheimer's Disease: Mechanisms and Therapeutic Strategies

2018 ◽  
Vol 15 (3) ◽  
pp. 283-300 ◽  
Author(s):  
Yu Gao ◽  
Lin Tan ◽  
Jin-Tai Yu ◽  
Lan Tan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Therapeutic Strategy ◽  
Recent Literature ◽  
Neurodegenerative Disorder ◽  
Therapeutic Strategies ◽  
Behavioral Disabilities ◽  
Disease Mechanisms ◽  
Immunization Strategies

Objective: Alzheimer's disease (AD), the most important progressive neurodegenerative disorder, is characterized by cognitive and behavioral disabilities. Nowadays, tau, as a microtubuleassociated protein and a principle neuropathological hallmark of AD, provides us a neoteric perspective to explore further aetiopathogenesis and therapeutic strategy. The hyperphosphorylation and abnormal aggregation of tau, combined with its decreased clearance, form neurofibrillary tangles (NFTs) and exert neurotoxicity in AD. Methods: Recent investigations aim to prevent the deposition of NFT and accelerate the clearance of NFT. Intriguingly, immunization strategies targeting tau effectively ameliorates the tau-associated pathology in AD. In addition, modified therapies targeting tau should be regarded as a potential way to treat AD. These progresses open new avenues for AD. Conclusion: Here, we review the recent literature of potential mechanisms of the tau in AD and discuss the modified therapeutic strategies for AD.

Sign in / Sign up

Export Citation Format

Share Document