scholarly journals Calpain Dysregulation in Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Adriana Ferreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Marked Decrease ◽  
Senile Plaques ◽  
Cysteine Proteases ◽  
Axonal Guidance ◽  
Cell Functions ◽  
Multiple Cell ◽  
Axonal Guidance Growth ◽  
Differentiation And Proliferation

Alzheimer’s disease (AD) is characterized by the presence of senile plaques and neurofibrillary tangles in the neocortex and hippocampus of AD patients. In addition, a marked decrease in synaptic contacts has been detected in these affected brain areas. Due to its prevalence in the aging population, this disease has been the focus of numerous studies. The data obtained from those studies suggest that the mechanisms leading to the formation of the hallmark lesions of AD might be linked. One of such mechanisms seems to be the dysregulation of calcium homeostasis that results in the abnormal activation of calpains. Calpains are a family of Ca2+-dependent cysteine proteases that play a key role in multiple cell functions including cell development, differentiation and proliferation, axonal guidance, growth cone motility, and cell death, among others. In this paper, we briefly reviewed data on the structure of these proteases and their regulation under normal conditions. We also summarized data underscoring the participation of calpains in the neurodegenerative mechanisms associated with AD.

scholarly journals Antioxidant Therapies for Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Ye Feng ◽  
Xiaochuan Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Senile Plaques ◽  
Toxic Substances ◽  
Synaptic Loss ◽  
Recent Developments ◽  
Multiple Cell ◽  
Future Potential ◽  
And Behavior

Alzheimer’s disease (AD) is the most common neurodegenerative disease featuring progressive impairments in memory, cognition, and behavior and ultimately leads to death. The histopathological changes of Alzheimer’s disease include neuronal and synaptic loss, formation of extracellular senile plaques and intracellular neurofibrillary tangles in brain. Multiple lines of evidence indicate that oxidative stress not only strongly participates in an early stage of Alzheimer’s disease prior to cytopathology, but plays an important role in inducing and activating multiple cell signaling pathways that contribute to the lesion formations of toxic substances and then promotes the development of Alzheimer’s disease. Many years of studies show that antioxidant therapies have enjoyed general success in preclinical studies. Therefore, this paper mainly focuses on the recent developments of common used antioxidant therapies for Alzheimer’s disease and thus provides indications for future potential antioxidant therapeutic strategies of neurodegenerative diseases.

scholarly journals The impact of melatonin on antioxidant defense mechanisms in Alzheimer’s disease

2018 ◽  
Vol 72 ◽  
pp. 1114-1122
Author(s):  
Daria Malicka ◽  
Dominika Markowska ◽  
Jarosław Nuszkiewicz ◽  
Karolina Szewczyk-Golec
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Defense Mechanisms ◽  
Senile Plaques ◽  
Biological Clock ◽  
Cell Functions ◽  
Increased Risk ◽  
The Impact ◽  
Phosphorylated Tau Protein

During aging, the increased risk of neurodegenerative disease development is observed. One of the most common and most serious disorders is Alzheimer’s disease manifested by the loss of nerve cell functions. In the course of the disease, extracellular senile plaques consisting of beta-amyloid and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein are formed. As a result of aging, the repair potential of damaged nerve cells is reduced. Free radicals formed in excess generate augmented oxidative stress, which contributes to the damaging of biomolecules and the development of pathological changes. This mechanism is favored by a decrease in the efficiency of antioxidant enzymes and the deficiency of antioxidants, observed in aging organism. With age, the secretion of the pineal hormone melatonin, functioning as a biochemical biological clock, is significantly reduced. This compound has been proved to be a very effective antioxidant that plays a key role in protecting cells against excessive damage, especially in nervous tissue. Studies have shown that supplementation with exogenous melatonin can prevent oxidative stress-induced degeneration of neurons. Considering the action of melatonin and the pathogenesis of Alzheimer’s disease, the idea of using the hormone supplementation in the prevention and alleviation of the effects of the disease seems to be extremely interesting.

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

The Phosphoinositide Signal Transduction Pathway in the Pathogenesis of Alzheimer’s Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 355-362 ◽  
Author(s):  
Vincenza Rita Lo Vasco
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signal Transduction ◽  
Membrane Trafficking ◽  
Hormone Secretion ◽  
Signal Transduction Pathway ◽  
Brain Morphology ◽  
Signal Transduction Pathways ◽  
Transduction Pathway ◽  
Cell Functions

Background: During aging and in age-associated disorders, such as Alzheimer's Disease (AD), learning abilities decline. Probably, disturbances in signal transduction in brain cells underlie the cognitive decline. The phosphorylation/dephosphorylation imbalance occurring in degenerating neurons was recently related to abnormal activity of one or more signal transduction pathways. AD is known to be associated with altered neuronal Ca<sup>2+</sup> homeostasis, as Ca<sup>2+</sup> accumulates in affected neurons leading to functional impairment. It is becoming more and more evident the involvement of signal transduction pathways acting upon Ca<sup>2+</sup> metabolism and phosphorylation regulation of proteins. A growing interest raised around the role of signal transduction systems in a number of human diseases including neurodegenerative diseases, with special regard to the systems related to the phosphoinositide (PI) pathway and AD. The PI signal transduction pathway plays a crucial role, being involved in a variety of cell functions, such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, cytoskeleton regulation, cell cycle control, apoptosis, cell and tissue polarity, and contributes to regulate the Ca<sup>2+</sup> levels in the nervous tissue. Conclusion: A number of observations indicated that PI-specific phospholipase C (PLC) enzymes might be involved in the alteration of neurotransmission. To understand the role and the timing of action of the signalling pathways recruited during the brain morphology changes during the AD progression might help to elucidate the aetiopathogenesis of the disease, paving the way to prognosis refinement and/or novel molecular therapeutic strategies.

Biological Signatures of Alzheimer’s Disease

2020 ◽  
Vol 20 (9) ◽  
pp. 770-781 ◽  
Author(s):  
Poornima Sharma ◽  
Anjali Sharma ◽  
Faizana Fayaz ◽  
Sharad Wakode ◽  
Faheem H. Pottoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Senile Plaque ◽  
Senile Plaques ◽  
Amyloid Deposition ◽  
Immune Defense ◽  
Amyloid Angiopathy ◽  
Microvascular Changes ◽  
Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease

2020 ◽  
Vol 20 (26) ◽  
pp. 2380-2390 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Abdullah Al Mamun ◽  
Md. Ataur Rahman ◽  
Tapan Behl ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Misfolding ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Misfolded Proteins ◽  
Cell Organelles ◽  
The Impact

Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD. Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now. Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.

scholarly journals NLRP3 Inflammasome: A Starring Role in Amyloid-β- and Tau-Driven Pathological Events in Alzheimer’s Disease

2021 ◽  
pp. 1-22
Author(s):  
Mariana Van Zeller ◽  
Diogo M. Dias ◽  
Ana M. Sebastião ◽  
Cláudia A. Valente
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Neurofibrillary Tangles ◽  
Nlrp3 Inflammasome ◽  
Neuronal Death ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Wide Range

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease commonly diagnosed among the elderly population. AD is characterized by the loss of synaptic connections, neuronal death, and progressive cognitive impairment, attributed to the extracellular accumulation of senile plaques, composed by insoluble aggregates of amyloid-β (Aβ) peptides, and to the intraneuronal formation of neurofibrillary tangles shaped by hyperphosphorylated filaments of the microtubule-associated protein tau. However, evidence showed that chronic inflammatory responses, with long-lasting exacerbated release of proinflammatory cytokines by reactive glial cells, contribute to the pathophysiology of the disease. NLRP3 inflammasome (NLRP3), a cytosolic multiprotein complex sensor of a wide range of stimuli, was implicated in multiple neurological diseases, including AD. Herein, we review the most recent findings regarding the involvement of NLRP3 in the pathogenesis of AD. We address the mechanisms of NLRP3 priming and activation in glial cells by Aβ species and the potential role of neurofibrillary tangles and extracellular vesicles in disease progression. Neuronal death by NLRP3-mediated pyroptosis, driven by the interneuronal tau propagation, is also discussed. We present considerable evidence to claim that NLRP3 inhibition, is undoubtfully a potential therapeutic strategy for AD.

scholarly journals Exploitation of Marine Molecules to Manage Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 373
Author(s):  
Marisa Silva ◽  
Paula Seijas ◽  
Paz Otero
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Nmda Receptor Antagonists ◽  
Average Life ◽  
Average Life Expectancy ◽  
Large Reservoir ◽  
Drug Candidates ◽  
Neurodegenerative Process ◽  
Main Action

Neurodegenerative diseases are sociosanitary challenges of today, as a result of increased average life expectancy, with Alzheimer’s disease being one of the most prevalent. This pathology is characterized by brain impairment linked to a neurodegenerative process culminating in cognitive decline and behavioral disorders. Though the etiology of this pathology is still unknown, it is usually associated with the appearance of senile plaques and neurofibrillary tangles. The most used prophylaxis relies on anticholinesterase drugs and NMDA receptor antagonists, whose main action is to relieve symptoms and not to treat or prevent the disease. Currently, the scientific community is gathering efforts to disclose new natural compounds effective against Alzheimer’s disease and other neurodegenerative pathologies. Marine natural products have been shown to be promising candidates, and some have been proven to exert a high neuroprotection effect, constituting a large reservoir of potential drugs and nutraceutical agents. The present article attempts to describe the processes of extraction and isolation of bioactive compounds derived from sponges, algae, marine bacteria, invertebrates, crustaceans, and tunicates as drug candidates against AD, with a focus on the success of pharmacological activity in the process of finding new and effective drug compounds.

scholarly journals Increased Cerebrospinal Fluid Production as a Possible Mechanism Underlying Caffeine's Protective Effect against Alzheimer's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Peter Wostyn ◽  
Debby Van Dam ◽  
Kurt Audenaert ◽  
Peter Paul De Deyn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Senile Plaques ◽  
Protective Effects ◽  
Caffeine Consumption ◽  
Neuroprotective Effects ◽  
Csf Production

Alzheimer's disease (AD), the most common type of dementia among older people, is characterized by the accumulation of β-amyloid (Aβ) senile plaques and neurofibrillary tangles composed of hyperphosphorylated tau in the brain. Despite major advances in understanding the molecular etiology of the disease, progress in the clinical treatment of AD patients has been extremely limited. Therefore, new and more effective therapeutic approaches are needed. Accumulating evidence from human and animal studies suggests that the long-term consumption of caffeine, the most commonly used psychoactive drug in the world, may be protective against AD. The mechanisms underlying the suggested beneficial effect of caffeine against AD remain to be elucidated. In recent studies, several potential neuroprotective effects of caffeine have been proposed. Interestingly, a recent study in rats showed that the long-term consumption of caffeine increased cerebrospinal fluid (CSF) production, associated with the increased expression of Na+-K+ATPase and increased cerebral blood flow. Compromised function of the choroid plexus and defective CSF production and turnover, with diminished clearance of Aβ, may be one mechanism implicated in the pathogenesis of late-onset AD. If reduced CSF turnover is a risk factor for AD, then therapeutic strategies to improve CSF flow are reasonable. In this paper, we hypothesize that long-term caffeine consumption could exert protective effects against AD at least in part by facilitating CSF production, turnover, and clearance. Further, we propose a preclinical experimental design allowing evaluation of this hypothesis.

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