Receptor-Interacting Protein Kinase 1 (RIPK1) as a Potential Therapeutic Target: An Overview of Its Possible Role in the Pathogenesis of Alzheimer's Disease

2019 ◽  
Vol 16 (10) ◽  
pp. 907-918
Author(s):  
Hong Hao Chan ◽  
Rhun Yian Koh ◽  
Chooi Ling Lim ◽  
Chee Onn Leong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Kinase ◽  
Neurodegenerative Disorder ◽  
Psychiatric Symptoms ◽  
Current Treatment ◽  
Interacting Protein ◽  
Amyloid Aβ ◽  
Cognition Impairment ◽  
Insight Into

Alzheimer’s Disease (AD) is an age-dependent neurodegenerative disorder, the most common type of dementia that is clinically characterized by the presence of beta-amyloid (Aβ) extracellularly and intraneuronal tau protein tangles that eventually leads to the onset of memory and cognition impairment, development of psychiatric symptoms and behavioral disorders that affect basic daily activities. Current treatment approved by the U.S Food and Drug Administration (FDA) for AD is mainly focused on the symptoms but not on the pathogenesis of the disease. Recently, receptor-interacting protein kinase 1 (RIPK1) has been identified as a key component in the pathogenesis of AD through necroptosis. Furthermore, genetic and pharmacological suppression of RIPK1 has been shown to revert the phenotype of AD and its mediating pathway is yet to be deciphered. This review is aimed to provide an overview of the pathogenesis and current treatment of AD with the involvement of autophagy as well as providing a novel insight into RIPK1 in reverting the progression of AD, probably through an autophagy machinery.

scholarly journals Effect of plant extracts on Alzheimer’s disease: An insight into therapeutic avenues

2011 ◽  
Vol 02 (01) ◽  
pp. 056-061 ◽  
Author(s):  
M Obulesu ◽  
Dowlathabad Muralidhara Rao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Ache Inhibition ◽  
Melissa Officinalis ◽  
Lemon Balm ◽  
Aggregation Effect ◽  
Insight Into ◽  
Maidenhair Tree

ABSTRACTAlzheimer’s disease (AD) is a devastative neurodegenerative disorder which needs adequate studies on effective treatment options. The extracts of plants and their effect on the amelioration of AD symptoms have been extensively studied. This paper summarizes the mechanisms like acetylcholinesterase (AChE) inhibition, modifi cation of monoamines, antiamyloid aggregation effect, and antioxidant activity which are actively entailed in the process of amelioration of AD symptoms. These effects are induced by extracts of a few plants of different origin like Yizhi Jiannao, Moringaoleifera (Drumstick tree), Ginkgo Biloba (Ginkgo/Maidenhair tree), Cassia obtisufolia (Sicklepod), Desmodium gangeticum (Sal Leaved Desmodium), Melissa officinalis (Lemon Balm), and Salvia officinalis (Garden sage, common sage).

scholarly journals Dendritic spines are lost in clusters in Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Joana B. Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Memory Storage ◽  
Excitatory Synapses ◽  
Tau Pathology ◽  
Insight Into

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.

scholarly journals Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease

2022 ◽  
Vol 14 ◽  
Author(s):  
Zhen Lan ◽  
Yanting Chen ◽  
Jiali Jin ◽  
Yun Xu ◽  
Xiaolei Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Biological Functions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Insight Into

Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60–80% of cases. The pathogenesis of AD remains unclear, and no curative treatment is available so far. Increasing evidence has revealed a vital role of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in AD. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation. This review describes the biological functions and mechanisms of lncRNAs in AD, indicating that lncRNAs may provide potential therapeutic targets for the diagnosis and treatment of AD.

scholarly journals Dendritic spines are lost in clusters in patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Joana B. Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Memory Storage ◽  
Excitatory Synapses ◽  
Tau Pathology ◽  
Insight Into

SUMMARYAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau protein in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in patients with AD are still unclear. Here, comparing dendrites with and without tau pathology of AD patients, we show that the presence of tau pathology determines the loss of dendritic spines in blocks, ruling out alternative models where spine loss occurs randomly. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits by altering spine organization.

scholarly journals Alzheimer’s disease: new concepts on the role of autoimmunity and of NLRP3 inflammasome in the pathogenesis of the disease

2020 ◽  
Vol 18 ◽  
Author(s):  
Cinzia Severini ◽  
Christian Barbato ◽  
Maria Grazia Di Certo ◽  
Francesca Gabanella ◽  
Carla Petrella ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Critical Factor ◽  
Innate Immune Responses ◽  
New Concepts ◽  
Amyloid Aβ

: Alzheimer’s disease (AD), recognized as the most common neurodegenerative disorder, is clinically characterized by the presence of extracellular beta amyloid (Aβ) plaques and by intracellular neurofibrillary tau tangles, accompanied by glial activation and neuroinflammation. Increasing evidence suggests that self-misfolded proteins stimulate an immune response mediated by glial cells, inducing release of inflammatory mediators and the recruitment of peripheral macrophages into the brain, which in turn aggravate AD pathology. Aim of the present review is to update the current knowledge on the role of autoimmunity and neuroinflammation in the pathogenesis of the disease, indicating new target for therapeutic intervention. We mainly focused on the NLRP3 microglial inflammasome as a critical factor in stimulating innate immune responses, thus sustaining chronic inflammation. Additionally, we discussed the involvement of the NLRP3 inflammasome in the gut-brain axis. Direct targeting the NLRP3 inflammasome and the associated receptors could be a potential pharmacological strategy, since its inhibition would selectively reduce AD neuroinflammation.

scholarly journals Application of CRISPR/Cas9 in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Likui Lu ◽  
Xi Yu ◽  
Yongle Cai ◽  
Miao Sun ◽  
Hao Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Complex Disease ◽  
Neurodegenerative Disorder ◽  
Target Therapy ◽  
Abnormal Behavior ◽  
Psychological Suffering ◽  
Pathogenic Genes ◽  
Hyperphosphorylated Tau Protein ◽  
Amyloid Aβ

Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder clinically characterized by cognitive impairment, abnormal behavior, and social deficits, which is intimately linked with excessive β-amyloid (Aβ) protein deposition along with many other misfolded proteins, neurofibrillary tangles formed by hyperphosphorylated tau protein aggregates, and mitochondrial damage in neurons, leading to neuron loss. Currently, research on the pathological mechanism of AD has been elucidated for decades, still no effective treatment for this complex disease was developed, and the existing therapeutic strategies are extremely erratic, thereby leading to irreversible and progressive cognitive decline in AD patients. Due to gradually mental dyscapacitating of AD patients, AD not only brings serious physical and psychological suffering to patients themselves, but also imposes huge economic burdens on family and society. Accordingly, it is very imperative to recapitulate the progress of gene editing-based precision medicine in the emerging fields. In this review, we will mainly focus on the application of CRISPR/Cas9 technique in the fields of AD research and gene therapy, and summarize the application of CRISPR/Cas9 in the aspects of AD model construction, screening of pathogenic genes, and target therapy. Finally, the development of delivery systems, which is a major challenge that hinders the clinical application of CRISPR/Cas9 technology will also be discussed.

PLGA-Based Curcumin Delivery System: An Interesting Therapeutic Approach in Treatment of Alzheimer’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Sanaz Keshavarz Shahbaz ◽  
Khadijeh Koushki ◽  
Thozhukat Sathyapalan ◽  
Muhammed Majeed ◽  
Amirhossein Sahebkar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurological Disorders ◽  
Neurodegenerative Disorder ◽  
Aqueous Solubility ◽  
Plga Nanoparticles ◽  
Progressive Degeneration ◽  
Hyperphosphorylated Tau Protein ◽  
Amyloid Aβ ◽  
Β Amyloid

: Progressive degeneration and dysfunction of the nervous system because of oxidative stress, aggregations of misfolded proteins, and neuroinflammation are the key pathological features of neurodegenerative diseases. Alzheimer's disease is a chronic neurodegenerative disorder driven by uncontrolled extracellular deposition of β-amyloid (Aβ) in the amyloid plaques and intracellular accumulation of hyperphosphorylated tau protein. Curcumin is a hydrophobic polyphenol with noticeable neuroprotective and anti-inflammatory effects that can cross the blood-brain barrier. Therefore, it is widely studied for the alleviation of inflammatory and neurological disorders. However, the clinical application of curcumin is limited due to its low aqueous solubility and bioavailability. Recently, nano-based curcumin delivery systems are developed to overcome these limitations effectively. This review article discusses the effects and potential mechanisms of curcumin-loaded PLGA nanoparticles in Alzheimer’s disease.

scholarly journals Memory Enhancing Activity of Saraswatarishta in Mice

2020 ◽  
Vol 13 (4) ◽  
pp. 2033-2039
Author(s):  
Bhagyashri D. Rajopadhye ◽  
Ranjana A. Sahasrabudhe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Neurodegenerative Disorder ◽  
Disease Incidence ◽  
Preventive Measure ◽  
Current Treatment ◽  
Control Group ◽  
Group I ◽  
Memory Enhancing

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a gradual decline in memory. Incidence of Alzheimer's disease increases with age. The disease incidence is 1% in 60 year olds & increases to 30 % at 85 years age. Hence this disease is already having enormous magnitude in today's graying world. Current treatment of Alzheimer’s disease includes- cholinesterase inhibitors& N-methyl- D-aspartate antagonists, but the benefit observed is modest. In traditional medicine Saraswatarishta is being used as memory enhancer for centuries. Brahmi, one of its major ingredients, is also being used to treat Alzheimer’s. So present study was undertaken for authentication of traditional claims of Saraswatarishta as a memory-enhancing agent. Five groups of mice (6 mice in each) were used for this study. Control group (group I) received distilled water, Group II received Saraswatarishta (2.5ml/kg) single dose and Group III received Saraswatarishta (2.5ml/kg) for 2wks. Group IV was given Diazepam (1mg/kg) to produce amnesia. For Group V, Saraswatarishta (2.5ml/kg) was given for 2wks followed by Diazepam (1mg/kg). Effect of Saraswatarishta on learning and memory of mice was studied using elevated plus maze model (EPM). Reduction in TL (Transfer Latency) indicates improvement in learning or memory and prolongation indicates impairment. Diazepam induced prolongation of TL is an accepted model of dementia. In our study, 2 weeks daily treatment of Saraswatarishta completely prevented impairment of learning and memory by Diazepam, corroborating the Ayurvdic use of Saraswatarishta and Brahmi, its major ingredient in the management of dementia. Saraswatarishta can be used as preventive measure to overcome demensia in Alzheimer’s disease.

scholarly journals Contributions of Molecular and Optical Techniques to the Clinical Diagnosis of Alzheimer’s Disease

2020 ◽  
Vol 10 (11) ◽  
pp. 815
Author(s):  
Edoardo Bistaffa ◽  
Fabrizio Tagliavini ◽  
Paolo Matteini ◽  
Fabio Moda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Diagnosis ◽  
Neurodegenerative Disorder ◽  
Phenotypic Variability ◽  
Surface Enhanced Raman Spectroscopy ◽  
Reaction Products ◽  
Surface Enhanced Raman ◽  
Amyloid Aβ ◽  
Folded Proteins

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. The distinctive neuropathological feature of AD is the intracerebral accumulation of two abnormally folded proteins: β-amyloid (Aβ) in the form of extracellular plaques, and tau in the form of intracellular neurofibrillary tangles. These proteins are considered disease-specific biomarkers, and the definite diagnosis of AD relies on their post-mortem identification in the brain. The clinical diagnosis of AD is challenging, especially in the early stages. The disease is highly heterogeneous in terms of clinical presentation and neuropathological features. This phenotypic variability seems to be partially due to the presence of distinct Aβ conformers, referred to as strains. With the development of an innovative technique named Real-Time Quaking-Induced Conversion (RT-QuIC), traces of Aβ strains were found in the cerebrospinal fluid of AD patients. Emerging evidence suggests that different conformers may transmit their strain signature to the RT-QuIC reaction products. In this review, we describe the current challenges for the clinical diagnosis of AD and describe how the RT-QuIC products could be analyzed by a surface-enhanced Raman spectroscopy (SERS)-based systems to reveal the presence of strain signatures, eventually leading to early diagnosis of AD with the recognition of individual disease phenotype.

Sign in / Sign up

Export Citation Format

Share Document