The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer’s disease

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Yuan Zhang ◽  
Xu Chen ◽  
Yanfang Zhao ◽  
Murugavel Ponnusamy ◽  
Ying Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Degradation ◽  
Molecular Chaperones ◽  
Elderly Population ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Pathological Process ◽  
Β Amyloid

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly population. AD is associated with the buildup of β-amyloid and tau, which aggregate into extracellular plaques and neurofibrillary tangles. Although the exact mechanism of pathological process of AD is unclear, the dysfunction of protein degradation mechanisms has been proposed to play an important role in AD. The cellular degradation of abnormal or misfolded proteins consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy-lysosomal pathway (ALP), and interaction of molecular chaperones with UPS or ALP. Any disturbance to these systems causes proteins to accumulate, resulting in pathological process of AD. In this review, we summarize the knowledge of protein degradation pathways in the pathogenesis of AD in light of the current literature. In the future, the regulation UPS or ALP machineries could be the cornerstones of the treatment of AD.

Role of TREM2 in Alzheimer's Disease and its Consequences on β- Amyloid, Tau and Neurofibrillary Tangles

2020 ◽  
Vol 16 (13) ◽  
pp. 1216-1229 ◽  
Author(s):  
Anurag K. Singh ◽  
Gaurav Mishra ◽  
Anand Maurya ◽  
Rajendra Awasthi ◽  
Komal Kumari ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Tau Pathology ◽  
Functional Roles ◽  
Age Related ◽  
Β Amyloid ◽  
The Impact ◽  
Neuronal Stress

: Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on β-amyloid plaques and tau pathology in Alzheimer’s disease.

scholarly journals The Role of Mitochondria in Alzheimer’s Disease and its Potential Therapies

2020 ◽  
pp. 175-183
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Abilities ◽  
Metabolic Pathways ◽  
Elderly Population ◽  
The Elderly ◽  
Gradual Decline ◽  
Potential Therapeutic Target ◽  
Diet And Lifestyle

Alzheimer’s disease (AD) is a common form of dementia, affecting millions of people worldwide, mostly the elderly population. The gradual decline in cognitive functions, loss of memory, and sleep disorder are the most frequently reported in AD patients. Multiple studies have been carried out to find a potential therapeutic approach to prevent the progression of Alzheimer’s disease and increase the performance of cognitive abilities. Mitochondrial dysfunction leading to oxidative stress and other environmental factors, diet and lifestyle are the major risk factors. Mitochondria play an essential role and are a potential therapeutic target for treating and preventing AD progression. Various biochemical molecules involved in mitochondrial metabolic pathways are tested as directly acting on mitochondria. Numerous antioxidants are considered as a potential treatment for AD. Here, we highlighted the emerging mitochondrial base therapies and potent antioxidants that can be used in Alzheimer’s disease treatments.

scholarly journals Introducing New Neurons in the Alzheimer’s Disease Brain

2021 ◽  
Vol 7 (4) ◽  
pp. 1-6
Author(s):  
CA González ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Elderly Population ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
The Elderly ◽  
Cell Therapies ◽  
The Brain

Alzheimer’s disease is the most prevalent neurodegenerative disorder in the elderly population. The patients suffer cerebral atrophyas a consequence of extensive neuronal loss, especially in areas that play a role in memory and cognition. Cell therapies approaches have emerged as promising treatments to regenerate the brain tissue of the patients

scholarly journals The Role of Aβ in the Development of Alzheimer’s Disease and its Mechanisms

2020 ◽  
Vol 218 ◽  
pp. 03041
Author(s):  
Yifei Jin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Clinical Symptoms ◽  
Senile Plaques ◽  
The Elderly ◽  
Aβ Peptides ◽  
Hyperphosphorylated Tau Protein ◽  
Neurodegenerative Dementia

Alzheimer’s disease (AD) is chronic neurodegenerative dementia representing the most common cause of dementia in the elderly population. It is a major source of morbidity, mortality, and healthcare expenditure worldwide. Although the molecular and cellular properties related to AD have been demonstrated decades before the onset of clinical symptoms, AD’s pathogenesis is still unknown as a combination of risk factors causes it. Today, pathogenesis theories focused on senile plaques (SP) formed by the extracellular accumulation and deposition of Aβ peptides and neurofibrillary tangles (NFTs), which are composed of the hyperphosphorylated tau protein. Furthermore, growing evidence points out that toxic Aβ plays a primary causal role in the induction and transmission of pathology and neuronal dysfunction and loss. Therefore, Aβ is crucial to the development of AD and is a noteworthy issue in AD research. This review shows the formation of Aβ and the differences of cytotoxicity of its various isoforms and aggregation states. It also summarizes the mechanisms by which Aβ induce AD through its neurotoxicity and state how these mechanisms interact and reinforce each other.

scholarly journals A novel view on Alzheimer’s disease pathogenesis: modern conceptof amyloid clearance

2018 ◽  
pp. 22-28
Author(s):  
V. Yu. Lobzin ◽  
K. A. Kolmakova ◽  
A. Yu. Emelin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
The Elderly ◽  
Perivascular Spaces ◽  
Vascular Risk ◽  
Common Cause ◽  
Β Amyloid ◽  
The Brain

Alzheimer’s disease is the most common cause of dementia among the elderly. Te pathological changes characterize by the deposition of amyloid plaques and the formation of neurofybrillar tangles in the brain. Te most signifcant role in the pathogenesis of neurodegeneration development is deposition of β-amyloid, vascular risk factors, the presence of a genetic predisposition, and the dysregulation of the bloodbrain barrier. Recent studies have demonstrated the role of the glymphatic system in the clearance of betaamyloid through the perivascular spaces of Virchow-Robin.

Microglia in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Patrick Süß ◽  
Johannes C.M. Schlachetzki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Disease Stage ◽  
Disease Modifying Therapy ◽  
Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

scholarly journals Isovitexin modulates autophagy in Alzheimer’s disease via miR-107 signalling

2020 ◽  
Vol 11 (1) ◽  
pp. 391-401
Author(s):  
Jiang Cheng ◽  
Guowei Wang ◽  
Na Zhang ◽  
Fang Li ◽  
Lina Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Loss ◽  
The Elderly ◽  
Tnf Α ◽  
Autophagic Process ◽  
Molecular Signals ◽  
Ad Mouse Model ◽  
Mtor Signalling

AbstractBackground:Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.Methods:Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.Results:The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.Conclusion:This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.

scholarly journals Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Corona Solana ◽  
Raquel Tarazona ◽  
Rafael Solana
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Lymphoid Cells ◽  
Target Cells ◽  
The Brain

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

scholarly journals APOE-ε4 polymorphism and cognitive deficit among the elderly population of Fernando de Noronha

2008 ◽  
Vol 66 (2b) ◽  
pp. 298-302 ◽  
Author(s):  
Anália Nusya Garcia ◽  
Helker Albuquerque da Silva ◽  
Renan Carlos Silva ◽  
Eliane Maria Medeiros Leal ◽  
Lorena Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Elderly Population ◽  
Cognitive Deficit ◽  
The Elderly ◽  
Clock Drawing Test ◽  
Apoe Ε4 ◽  
Pcr Rflp ◽  
Fernando De Noronha ◽  
Ε4 Allele

BACKGROUND: Polymorphism of the gene for apolipoprotein E (APOE) is an important risk factor for the development of Alzheimer's disease. The ε4 allele of the APOE gene has been linked with a number of neuropsychiatric illnesses, and also with stress and depression among geriatric populations. OBJECTIVE: To identify APOE-ε4 polymorphism and correlate this with cognitive deficit among the elderly population of the island of Fernando de Noronha. METHOD: Neuropsychiatric tests (mini-mental state examination, verbal fluency test and clock drawing test) were applied to 52 elderly people without Alzheimer's disease. DNA was isolated from peripheral blood and genotyping of APOE was done by the PCR-RFLP method. RESULTS: 87% of the elderly population (mean age 69.6±7.0) had cognitive deficit. CONCLUSION: The observed frequency of the ε4 allele was 10%, but the correlation between the presence of ε4 and cognitive deficit in this population was not statistically significant.

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