An Insight into the Molecular and Therapeutic Targets of Amyloid Plaques in Alzheimer's Disease and an Update on the Prospects of Drugs in Research

Alzheimer’s disease (AD) is characterized by progressive loss of cognition and a gradual decrease in memory. Though AD is considered the most persistent form of dementia and a global concern, no complete cure or agents that can completely halt the progression of AD have been found. In the past years, considerable advancements in the understanding of cellular and molecular changes associated with AD has been investigated and numerous pharmacological targets have been recognized to enable drug development for the condition. Amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) are the major attributes of AD. Symptomatic relief is the only possible treatment available at present and a disease modifying drug is of utmost importance. Development of drugs that can inhibit different targets responsible for the formation of plaques is a potential area in AD research. This review is not a complete list of all possible targets for AD but serves to highlight the targets related to amyloid pathology and pathway concerned with the formation of amyloid fragments. This shall serve as a prospect in identification of amyloid plaque inhibitors and pave the strategies for newer drug treatments. Nevertheless, substantial research is done in this area but to bridle, the clinical difficulty remains a concern.

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An insight into the role of Artificial Intelligence in the early diagnosis of Alzheimer’s disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527320666210512014505 ◽

2021 ◽

Vol 20 ◽

Author(s):

Rohit Kumar Verma ◽

Manisha Pandey ◽

Pooja Chawla ◽

Hira Choudhury ◽

Jayashree Mayuren ◽

...

Keyword(s):

Artificial Intelligence ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Diagnosis ◽

Symptomatic Relief ◽

Large Data ◽

Successful Implementation ◽

Clinical Implementation ◽

Insight Into

Background: The complication of Alzheimer’s disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the foremost hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated. Method: To overcome the limitation, the use of artificial intelligence along with technical tools has been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review. Conclusion: Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.

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Molecular Targets in Alzheimer’s Disease: From Pathogenesis to Therapeutics

BioMed Research International ◽

10.1155/2015/760758 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Xuan Cheng ◽

Lu Zhang ◽

Ya-Jun Lian

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Signaling Pathways ◽

Therapeutic Strategy ◽

Tea Polyphenols ◽

Pharmacological Targets ◽

Drug Designing ◽

Multiple Health ◽

Insight Into ◽

Cell Signaling Pathways

Alzheimer’s disease(AD) is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories. Nonavailability of definitive therapeutic strategy urges developing pharmacological targets based on cell signaling pathways. A great revival of interest in nutraceuticals and adjuvant therapy has been put forward. Tea polyphenols for their multiple health benefits have also attracted the attention of researchers. Tea catechins showed enough potentiality to be used in future as therapeutic targets to provide neuroprotection against AD. This review attempts to present a concise map of different receptor signaling pathways associated with AD with an insight into drug designing based on the proposed signaling pathways, molecular mechanistic details of AD pathogenesis, and a scientific rationale for using tea polyphenols as proposed therapeutic agents in AD.

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Voxel-based morphometry (VBM) analysis in Alzheimer's disease an insight into heterogeneity of cerebral atrophy

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0338 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S338-S338

Author(s):

Akihiko Shiino ◽

Toshiyuki Watanabe ◽

Ichiro Akiguchi ◽

Shigehiro Morikawa ◽

Toshiro Inubushi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebral Atrophy ◽

Voxel Based Morphometry ◽

Insight Into

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Faculty Opinions recommendation of Aspirin induces lysosomal biogenesis and attenuates amyloid plaque pathology in a mouse model of alzheimer's disease via pparα.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733575200.793548126 ◽

2018 ◽

Author(s):

Thierry Galli ◽

Alessandra Gallo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Amyloid Plaque ◽

Model Of Alzheimer’S Disease ◽

Plaque Pathology

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Insight into the Epigenetics of Alzheimer's Disease: A Computational Study from Human Interactome

Current Alzheimer Research ◽

10.2174/1567205013666160803151101 ◽

2016 ◽

Vol 13 (12) ◽

pp. 1385-1396 ◽

Cited By ~ 4

Author(s):

Paulami Chatterjee ◽

Debjani Roy

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Computational Study ◽

Human Interactome ◽

Insight Into

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

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200422105156 ◽

2020 ◽

Vol 20 (13) ◽

pp. 1214-1234 ◽

Cited By ~ 4

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.

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Current Strategies and Novel Drug Approaches for Alzheimer Disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200717091513 ◽

2020 ◽

Vol 19 (9) ◽

pp. 676-690 ◽

Cited By ~ 2

Author(s):

Roma Ghai ◽

Kandasamy Nagarajan ◽

Meenakshi Arora ◽

Parul Grover ◽

Nazakat Ali ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholinergic Neurons ◽

Amyloid Plaque ◽

Neural Pathways ◽

Current Trends ◽

Personality Changes ◽

Traditional Therapies ◽

Novel Drug ◽

The Brain

Alzheimer’s Disease (AD) is a chronic, devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured, but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc. are being used to manage the symptoms of Alzheimer’s disease. The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Enormous literature survey was conducted and published articles of PubMed, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

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Nanotechnology Based Delivery Systems of Drugs Currently Used to Treat Alzheimer’s Disease

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681209666190228143636 ◽

2020 ◽

Vol 10 (3) ◽

pp. 228-247

Author(s):

Niloufar Choubdar ◽

Sara Avizheh

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Polymeric Nanoparticles ◽

Biological Fluids ◽

Delivery Systems ◽

Original Research ◽

Sustained Drug Release ◽

The Past ◽

Site Of Action ◽

Therapeutic Compound

Alzheimer’s Disease (AD) is one of the most common forms of dementia affecting over 46 million people, according to AD International. Over the past few decades, there has been considerable interest in developing nanomedicines. Using nanocarriers, the therapeutic compound could be delivered to the site of action where it gets accumulated. This accumulation, therefore, reduces the required doses for therapy. Alternatively, using nanocarriers decreases the side effects. Nanotechnology has had a great contribution in developing Drug Delivery Systems (DDS). These DDS could function as reservoirs for sustained drug release or control the pharmacokinetics and biodistribution of the drugs. In the current review, we have collected 38 original research articles using nanotechnology as DDS for the clinically used cholinesterase inhibitor drugs donepezil (DPZ), Rivastigmine (Riv), and galantamine (Gal) used for AD treatment from 2002 to 2017 from Scopus and PubMed databases. Regarding DDS used for DPZ, most of the research in recent years dealt with polymeric nanoparticles (NPs) including Poly-D, L-Lactide-Co-Glycolide (PLGA), and chitosans (CHs), then Liposomes (LPs), nanogels, and natural products, respectively. In terms of Riv most of the research performed was focused on polymeric NPs including PLGA, polylactic acid (PLA), Poly-Ε-Caprolactone (PCL), poly-alkyl-cyanoacrylates, CH, gelatin and then LPs. The highest application of NPs in regard to Gal was related to modified LPs and polymeric NPs. Polymeric NPs demonstrate safety, higher stability in biological fluids and against enzymatic metabolism, biocompatibility, bioavailability, and improved encapsulation efficacy. LPs, another major delivery system used, demonstrate biocompatibility, ease of surface modification, and amphiphilic nature.

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Continuous and Cyclic Progesterone Differentially Interact with Estradiol in the Regulation of Alzheimer-Like Pathology in Female 3×Transgenic-Alzheimer’s Disease Mice

Endocrinology ◽

10.1210/en.2009-1487 ◽

2010 ◽

Vol 151 (6) ◽

pp. 2713-2722 ◽

Cited By ~ 57

Author(s):

Jenna C. Carroll ◽

Emily R. Rosario ◽

Angela Villamagna ◽

Christian J. Pike

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Postmenopausal Women ◽

Transgenic Mouse Model ◽

Dependent Behavior ◽

Potential Efficacy ◽

Increased Risk ◽

Neural Interactions ◽

Β Amyloid ◽

Insight Into

Depletion of estrogens and progesterone at menopause has been linked to an increased risk for the development of Alzheimer’s disease (AD) in women. A currently controversial literature indicates that although treatment of postmenopausal women with hormone therapy (HT) may reduce the risk of AD, several parameters of HT may limit its potential efficacy and perhaps, even exacerbate AD risk. One such parameter is continuous vs. cyclic delivery of the progestogen component of HT. Recent experimental evidence suggests that continuous progesterone can attenuate neural actions of estradiol (E2). In the present study, we compared the effects of continuous and cyclic progesterone treatment in the presence and absence of E2 in ovariectomized 3×Tg-AD mice, a transgenic mouse model of AD. We found that ovariectomy-induced hormone depletion increases AD-like pathology in female 3×Tg-AD mice, including accumulation of β-amyloid, tau hyperphosphorylation, and impaired hippocampal-dependent behavior. E2 treatment alone prevents the increases in pathology. Continuous progesterone did not affect β-amyloid levels when delivered alone but blocked the Aβ-lowering action of E2. In contrast, cyclic progesterone significantly reduced β-amyloid levels by itself and enhanced rather than inhibited the E2 effects. These results provide new insight into the neural interactions between E2 and progesterone that may prove valuable in optimizing HT regimens in postmenopausal women.

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