Comprehensive review on Alzheimer's Disease: Pathophysiology and its Treatment

2021 ◽  
Vol 4 (3) ◽  
pp. 3-12
Author(s):  
Prativa Sadhu ◽  
◽  
Srijani Sen ◽  
Catherine Vanlalhriatpuii ◽  
◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Signs ◽  
Acetylcholinesterase Inhibitors ◽  
Neuron Activity ◽  
Aβ Peptides ◽  
Comprehensive Review ◽  
Thinking Ability ◽  
The Cost ◽  
Amyloid Cascade

Neurodegenerative disorders are marked by the loss of brain neuron activity, resulting in gradual cognitive impairment. The effects of neurodegenerative diseases are severe in terms of pathology and the cost of patient care. The aged, in general, are the most vulnerable. Alzheimer's disease (AD) is a brain ailment that causes cell degradation and is the leading cause of dementia, identified by a loss of thinking ability and independence in daily tasks. The amyloid cascade hypothesis, which attributes clinical signs/symptoms to an abundance of amyloid-beta (Aβ) peptides, enhanced deposition into amyloid plaques, and eventually neuronal destruction, is one theory for pathogenesis AD. The use of acetylcholinesterase inhibitors in AD treatment is based on their favorable effects on the disease's functional, cognitive and behavioral symptoms. However, their involvement in AD pathogenesis is uncertain. This comprehensive review will provide an overview of AD, including the pathophysiology, causes, treatments, and future treatment.

scholarly journals Intracellular Calcium Dysregulation by the Alzheimer’s Disease-Linked Protein Presenilin 2

2020 ◽  
Vol 21 (3) ◽  
pp. 770 ◽  
Author(s):  
Luisa Galla ◽  
Nelly Redolfi ◽  
Tullio Pozzan ◽  
Paola Pizzo ◽  
Elisa Greotti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Amyloid Β ◽  
Presenilin 1 ◽  
Calcium Dysregulation ◽  
Aβ Peptides ◽  
Functional Consequences ◽  
Presenilin 2 ◽  
Amyloid Cascade

Alzheimer’s disease (AD) is the most common form of dementia. Even though most AD cases are sporadic, a small percentage is familial due to autosomal dominant mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes. AD mutations contribute to the generation of toxic amyloid β (Aβ) peptides and the formation of cerebral plaques, leading to the formulation of the amyloid cascade hypothesis for AD pathogenesis. Many drugs have been developed to inhibit this pathway but all these approaches currently failed, raising the need to find additional pathogenic mechanisms. Alterations in cellular calcium (Ca2+) signaling have also been reported as causative of neurodegeneration. Interestingly, Aβ peptides, mutated presenilin-1 (PS1), and presenilin-2 (PS2) variously lead to modifications in Ca2+ homeostasis. In this contribution, we focus on PS2, summarizing how AD-linked PS2 mutants alter multiple Ca2+ pathways and the functional consequences of this Ca2+ dysregulation in AD pathogenesis.

Alzheimer’s Disease: Innovative Therapeutic Approaches Based on Peptides and Nanoparticles

2021 ◽  
pp. 107385842110164
Author(s):  
Isabela F. L. Mota ◽  
Larissa S. de Lima ◽  
Bruna de M. Santana ◽  
Giovanna de A. M. Gobbo ◽  
João V. M. L. Bicca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Options ◽  
Pharmaceutical Research ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Acetylcholinesterase Inhibitors ◽  
Low Toxicity ◽  
New Treatments ◽  
Amyloid Cascade

Alzheimer’s disease (AD) is the main cause of dementia in the world and its etiology is not yet fully understood. The pathology of AD is primarily characterized by intracellular neurofibrillary tangles and extracellular amyloid-β plaques. Unfortunately, few treatment options are available, and most treat symptoms, as is the case of acetylcholinesterase inhibitors (IAChE) and N-methyl-d-aspartate receptor antagonists. For more than 20 years pharmaceutical research has targeted the “amyloid cascade hypothesis,” but this has not produced meaningful results, leading researchers to focus now on other characteristics of the disease and on multitarget approaches. This review aims to evaluate some new treatments that are being developed and studied. Among these are new treatments based on peptides, which have high selectivity and low toxicity; however, these compounds have a short half-life and encounter challenges when crossing the blood-brain barrier. The present review discusses up-and-coming peptides tested as treatments and explores some nanotechnological strategies to overcome the downsides. These compounds are promising, as they not only act on the symptoms but also aim to prevent progressive neuronal loss.

Cognitive symptoms of Alzheimer’s disease: clinical management and prevention

BMJ ◽  
2019 ◽  
pp. l6217 ◽  
Author(s):  
Elizabeth Joe ◽  
John M Ringman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Acetylcholinesterase Inhibitors ◽  
Amyloid Cascade Hypothesis ◽  
Prodromal Ad ◽  
Disease Modifying ◽  
Medical Foods ◽  
Disease Modifying Treatment ◽  
Amyloid Cascade

ABSTRACTAlzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid β in the form of extracellular plaques and by intracellular neurofibrillary tangles, with eventual neurodegeneration and dementia. There is currently no disease-modifying treatment though several symptomatic medications exist with modest benefit on cognition. Acetylcholinesterase inhibitors have a consistent benefit across all stages of dementia; their benefit in mild cognitive impairment and prodromal AD is unproven. Memantine has a smaller benefit on cognition overall which is limited to the moderate to severe stages, and the combination of a cholinesterase inhibitor and memantine may have additional efficacy. Evidence for the efficacy of vitamin E supplementation and medical foods is weak but might be considered in the context of cost, availability, and safety in individual patients. Apparently promising disease-modifying interventions, mostly addressing the amyloid cascade hypothesis of AD, have recently failed to demonstrate efficacy so novel approaches must be considered.

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 cost-utility of the rivastigmine transdermal patch in the management of patients with moderate Alzheimer's disease in the US

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
A Brennan ◽  
B Nagy ◽  
A Brandtmüller ◽  
SK Thomas ◽  
M Gallagher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cost Utility ◽  
Transdermal Patch ◽  
The Us ◽  
The Cost

The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View

2018 ◽  
Vol 15 (13) ◽  
pp. 1191-1212 ◽  
Author(s):  
Botond Penke ◽  
Gábor Paragi ◽  
János Gera ◽  
Róbert Berkecz ◽  
Zsolt Kovács ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathways ◽  
Membrane Lipids ◽  
Specific Protein ◽  
Dietary Factors ◽  
Lipid Signaling ◽  
Special Role ◽  
Aβ Peptides

Lipids participate in Amyloid Precursor Protein (APP) trafficking and processing - important factors in the initiation of Alzheimer’s disease (AD) pathogenesis and influence the formation of neurotoxic β-amyloid (Aβ) peptides. An important risk factor, the presence of ApoE4 protein in AD brain cells binds the lipids to AD. In addition, lipid signaling pathways have a crucial role in the cellular homeostasis and depend on specific protein-lipid interactions. The current review focuses on pathological alterations of membrane lipids (cholesterol, glycerophospholipids, sphingolipids) and lipid metabolism in AD and provides insight in the current understanding of biological membranes, their lipid structures and functions, as well as their role as potential therapeutic targets. Novel methods for studying the membrane structure and lipid composition will be reviewed in a broad sense whereas the use of lipid biomarkers for early diagnosis of AD will be shortly summarized. Interactions of Aβ peptides with the cell membrane and different subcellular organelles are reviewed. Next, the details of the most important lipid signaling pathways, including the role of the plasma membrane as stress sensor and its therapeutic applications are given. 4-hydroxy-2-nonenal may play a special role in the initiation of the pathogenesis of AD and thus the “calpain-cathepsin hypothesis” of AD is highlighted. Finally, the most important lipid dietary factors and their possible use and efficacy in the prevention of AD are discussed.

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

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