scholarly journals Zinc-mediated Neurotransmission in Alzheimer's Disease: A Potential Role of the GPR39 in Dementia

2019 ◽  
Vol 18 (1) ◽  
pp. 2-13
Author(s):  
Michal Rychlik ◽  
Katarzyna Mlyniec
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Neural Plasticity ◽  
Modern Society ◽  
Neuroprotective Drugs ◽  
Age Related ◽  
Candidate Drug ◽  
G Protein Coupled

: With more people reaching an advanced age in modern society, there is a growing need for strategies to slow down age-related neuropathology and loss of cognitive functions, which are a hallmark of Alzheimer's disease. Neuroprotective drugs and candidate drug compounds target one or more processes involved in the neurodegenerative cascade, such as excitotoxicity, oxidative stress, misfolded protein aggregation and/or ion dyshomeostasis. A growing body of research shows that a G-protein coupled zinc (Zn2+) receptor (GPR39) can modulate the abovementioned processes. : Zn2+itself has a diverse activity profile at the synapse, and by binding to numerous receptors, it plays an important role in neurotransmission. However, Zn2+ is also necessary for the formation of toxic oligomeric forms of amyloid beta, which underlie the pathology of Alzheimer’s disease. Furthermore, the binding of Zn2+ by amyloid beta causes a disruption of zincergic signaling, and recent studies point to GPR39 and its intracellular targets being affected by amyloid pathology. : In this review, we present neurobiological findings related to Zn2+ and GPR39, focusing on its signaling pathways, neural plasticity, interactions with other neurotransmission systems, as well as on the effects of pathophysiological changes observed in Alzheimer's disease on GPR39 function. : Direct targeting of the GPR39 might be a promising strategy for the pharmacotherapy of zincergic dyshomeostasis observed in Alzheimer’s disease. The information presented in this article will hopefully fuel further research into the role of GPR39 in neurodegeneration and help in identifying novel therapeutic targets for dementia.

Alzheimer’s disease: as it was in the beginning

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Stanislav Kozlov ◽  
Alexei Afonin ◽  
Igor Evsyukov ◽  
Andrei Bondarenko
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Metal Ion ◽  
Aberrant Cell ◽  
Molecular Abnormalities ◽  
Model Of Alzheimer’S Disease ◽  
Age Related

AbstractSince Alzheimer’s disease was first described in 1907, many attempts have been made to reveal its main cause. Nowadays, two forms of the disease are known, and while the hereditary form of the disease is clearly caused by mutations in one of several genes, the etiology of the sporadic form remains a mystery. Both forms share similar sets of neuropathological and molecular manifestations, including extracellular deposition of amyloid-beta, intracellular accumulation of hyperphosphorylated tau protein, disturbances in both the structure and functions of mitochondria, oxidative stress, metal ion metabolism disorders, impairment of N-methyl-D-aspartate receptor-related signaling pathways, abnormalities of lipid metabolism, and aberrant cell cycle reentry in some neurons. Such a diversity of symptoms led to proposition of various hypotheses for explaining the development of Alzheimer’s disease, the amyloid hypothesis, which postulates the key role of amyloid-beta in Alzheimer’s disease development, being the most prominent. However, this hypothesis does not fully explain all of the molecular abnormalities and is therefore heavily criticized. In this review, we propose a hypothetical model of Alzheimer’s disease progression, assuming a key role of age-related mitochondrial dysfunction, as was postulated in the mitochondrial cascade hypothesis. Our model explains the connections between all the symptoms of Alzheimer’s disease, with particular attention to autophagy, metal metabolism disorders, and aberrant cell cycle re-entry in neurons. Progression of the Alzheimer’s disease appears to be a complex process involving aging and too many protective mechanisms affecting one another, thereby leading to even greater deleterious effects.

scholarly journals Inverse Correlation Between Alzheimer’s Disease and Cancer: Short Overview

2021 ◽  
Author(s):  
Agnieszka Zabłocka ◽  
Wioletta Kazana ◽  
Marta Sochocka ◽  
Bartłomiej Stańczykiewicz ◽  
Maria Janusz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kinase Inhibitor ◽  
Fungal Infections ◽  
Neurological Diseases ◽  
Inverse Correlation ◽  
Biological Mechanisms ◽  
Age Related ◽  
Common Risk Factors

AbstractThe negative association between Alzheimer’s disease (AD) and cancer suggests that susceptibility to one disease may protect against the other. When biological mechanisms of AD and cancer and relationship between them are understood, the unsolved problem of both diseases which still touches the growing human population could be overcome. Actual information about biological mechanisms and common risk factors such as chronic inflammation, age-related metabolic deregulation, and family history is presented here. Common signaling pathways, e.g., p53, Wnt, role of Pin1, and microRNA, are discussed as well. Much attention is also paid to the potential impact of chronic viral, bacterial, and fungal infections that are responsible for the inflammatory pathway in AD and also play a key role to cancer development. New data about common mechanisms in etiopathology of cancer and neurological diseases suggests new therapeutic strategies. Among them, the use of nilotinib, tyrosine kinase inhibitor, protein kinase C, and bexarotene is the most promising.

scholarly journals SPON1 Can Reduce Amyloid Beta and Reverse Cognitive Impairment and Memory Dysfunction in Alzheimer’s Disease Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1275
Author(s):  
Soo Yong Park ◽  
Joo Yeong Kang ◽  
Taehee Lee ◽  
Donggyu Nam ◽  
Chang-Jin Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Precursor Protein ◽  
Amyloid Beta ◽  
Physiological Activity ◽  
Precursor Protein ◽  
Age Related

Alzheimer’s disease (AD) is a complex, age-related neurodegenerative disease that is the most common form of dementia. However, the cure for AD has not yet been founded. The accumulation of amyloid beta (Aβ) is considered to be a hallmark of AD. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), also known as beta secretase is the initiating enzyme in the amyloidogenic pathway. Blocking BACE1 could reduce the amount of Aβ, but this would also prohibit the other functions of BACE1 in brain physiological activity. SPONDIN1 (SPON1) is known to bind to the BACE1 binding site of the amyloid precursor protein (APP) and blocks the initiating amyloidogenesis. Here, we show the effect of SPON1 in Aβ reduction in vitro in neural cells and in an in vivo AD mouse model. We engineered mouse induced neural stem cells (iNSCs) to express Spon1. iNSCs harboring mouse Spon1 secreted SPON1 protein and reduced the quantity of Aβ when co-cultured with Aβ-secreting Neuro 2a cells. The human SPON1 gene itself also reduced Aβ in HEK 293T cells expressing the human APP transgene with AD-linked mutations through lentiviral-mediated delivery. We also demonstrated that injecting SPON1 reduced the amount of Aβ and ameliorated cognitive dysfunction and memory impairment in 5xFAD mice expressing human APP and PSEN1 transgenes with five AD-linked mutations.

scholarly journals Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 968 ◽  
Author(s):  
Sunitha Kodidela ◽  
Kelli Gerth ◽  
Sanjana Haque ◽  
Yuqing Gong ◽  
Saifudeen Ismael ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Progressive Dementia ◽  
Hiv Patients ◽  
Age Related ◽  
Infected Cells ◽  
New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

scholarly journals Osmotin-loaded magnetic nanoparticles with electromagnetic guidance for the treatment of Alzheimer's disease

Nanoscale ◽  
2017 ◽  
Vol 9 (30) ◽  
pp. 10619-10632 ◽  
Author(s):  
Faiz Ul Amin ◽  
Ali Kafash Hoshiar ◽  
Ton Duc Do ◽  
Yeongil Noh ◽  
Shahid Ali Shah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Nanoparticles ◽  
Neurodegenerative Disease ◽  
Amyloid Beta ◽  
Age Related ◽  
Electromagnetic Guidance ◽  
The Brain

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain.

P4-036: Role of nitric oxide and arachidonic acid release and metabolism in Alzheimer's disease amyloid beta toxicity

2006 ◽  
Vol 2 ◽  
pp. S524-S524
Author(s):  
Joanna B. Strosznajder ◽  
Joanna Glowacka ◽  
Alicja Zabielna ◽  
Malgorzata Chalimoniuk
Keyword(s):  
Nitric Oxide ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Arachidonic Acid ◽  
Amyloid Beta ◽  
Arachidonic Acid Release ◽  
Acid Release

scholarly journals Overview of Alzheimer’s Disease and Some Therapeutic Approaches Targeting Aβby Using Several Synthetic and Herbal Compounds

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Sandeep Kumar Singh ◽  
Saurabh Srivastav ◽  
Amarish Kumar Yadav ◽  
Saripella Srikrishna ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Therapeutic Approaches ◽  
Age Related

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-βmetabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics.

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