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.

scholarly journals Protein-protein interactions in neurodegenerative diseases: a conspiracy theory

2020 ◽  
Author(s):  
Travis B. Thompson ◽  
Pavanjit Chaggar ◽  
Ellen Kuhl ◽  
Alain Goriely ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Amyloid Beta ◽  
Tau Protein ◽  
Conspiracy Theory ◽  
Tau Proteins ◽  
Disease Research ◽  
Protein Clearance ◽  
The Brain

AbstractNeurodegenerative diseases such as Alzheimer’s or Parkinson’s are associated with the prion-like propagation and aggregation of toxic proteins. A long standing hypothesis that amyloid-beta drives Alzheimer’s disease has proven the subject of contemporary controversy; leading to new research in both the role of tau protein and its interaction with amyloid-beta. Conversely, recent work in mathematical modeling has demonstrated the relevance of nonlinear reaction-diffusion type equations to capture essential features of the disease. Such approaches have been further simplified, to network-based models, and offer researchers a powerful set of computationally tractable tools with which to investigate neurodegenerative disease dynamics.Here, we propose a novel, coupled network-based model for a two-protein system that includes an enzymatic interaction term alongside a simple model of aggregate transneuronal damage. We apply this theoretical model to test the possible interactions between tau proteins and amyloid-beta and study the resulting coupled behavior between toxic protein clearance and proteopathic phenomenology. Our analysis reveals ways in which amyloid-beta and tau proteins may conspire with each other to enhance the nucleation and propagation of different diseases, thus shedding new light on the importance of protein clearance and protein interaction mechanisms in prion-like models of neurodegenerative disease.Author SummaryIn 1906 Dr. Alois Alzheimer delivered a lecture to the Society of Southwest German Psychiatrists. Dr. Alzheimer presented the case of Ms. Auguste Deter; her symptoms would help to define Alzheimer’s disease (AD). Over a century later, with an aging world population, AD is at the fore of global neurodegenerative disease research. Previously, toxic amyloid-beta protein (Aβ) was thought to be the primary driver of AD development. Recent research suggests that another protein, tau, plays a fundamental role. Toxic tau protein contributes to cognitive decline and appears to interact with toxic Aβ; research suggests that toxic Aβ may further increase the effects of toxic tau.Theoretical mathematical models are an important part of neurodegenerative disease research. Such models: enable extensible computational exploration; illuminate emergent behavior; and reduce research costs. We have developed a novel, theoretical mathematical model of two interacting species of proteins within the brain. We analyze the mathematical model and demonstrate a computational implementation in the context of Aβ-tau interaction in the brain. Our model clearly suggests that: the removal rate of toxic protein plays a critical role in AD; and the Aβ-tau ‘conspiracy theory’ is a nuanced, and exciting path forward for Alzheimer’s disease research.

scholarly journals Probable Causes of Alzheimer’s Disease

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 16
Author(s):  
James David Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lactic Acid ◽  
Blood Brain Barrier ◽  
Transient Receptor Potential ◽  
Brain Barrier ◽  
Folate Intake ◽  
Blood Brain ◽  
Age Related ◽  
The Brain

A three-part mechanism is proposed for the induction of Alzheimer’s disease: (1) decreased blood lactic acid; (2) increased blood ceramide and adipokines; (3) decreased blood folic acid. The age-related nature of these mechanisms comes from age-associated decreased muscle mass, increased visceral fat and changes in diet. This mechanism also explains why many people do not develop Alzheimer’s disease. Simple changes in lifestyle and diet can prevent Alzheimer’s disease. Alzheimer’s disease is caused by a cascade of events that culminates in damage to the blood–brain barrier and damage to neurons. The blood–brain barrier keeps toxic molecules out of the brain and retains essential molecules in the brain. Lactic acid is a nutrient to the brain and is produced by exercise. Damage to endothelial cells and pericytes by inadequate lactic acid leads to blood–brain barrier damage and brain damage. Inadequate folate intake and oxidative stress induced by activation of transient receptor potential cation channels and endothelial nitric oxide synthase damage the blood–brain barrier. NAD depletion due to inadequate intake of nicotinamide and alterations in the kynurenine pathway damages neurons. Changes in microRNA levels may be the terminal events that cause neuronal death leading to Alzheimer’s disease. A new mechanism of Alzheimer’s disease induction is presented involving lactic acid, ceramide, IL-1β, tumor necrosis factor α, folate, nicotinamide, kynurenine metabolites and microRNA.

scholarly journals Neurogenic responses to amyloid-beta plaques in the brain of Alzheimer’s disease-like transgenic (pPDGF-APPSw,Ind) mice

2008 ◽  
Vol 29 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Li Gan ◽  
Shuhong Qiao ◽  
Xun Lan ◽  
Liying Chi ◽  
Chun Luo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
The Brain

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 Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1572-1587 ◽  
Author(s):  
John D Arena ◽  
Douglas H Smith ◽  
Edward B Lee ◽  
Garrett S Gibbons ◽  
David J Irwin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Cell Types ◽  
Tau Pathology ◽  
Post Translational Modifications ◽  
Age Related ◽  
History Of ◽  
Severe Tbi

Abstract Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer’s disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer’s disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer’s disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer’s disease and ageing may rest solely on the pattern and distribution of pathology.

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.

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.

scholarly journals The Challenges of Diagnosis in Alzheimer’s Disease

US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 15 ◽  
Author(s):  
Nenad Bogdanovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Amyloid Pet ◽  
Positive Finding ◽  
Positron Emission ◽  
University Of Oslo ◽  
The University ◽  
Study Participants ◽  
The Brain

Current neuropathologic examination of the brain is still the gold standard for diagnosis of Alzheimer’s disease (AD). Postmortem studies, however, have indicated that current methods for the clinical diagnosis of AD are suboptimal.1Recent research has demonstrated the clinical utility of amyloid-beta positron emission tomography (PET) scans, which detect the presence of amyloid-beta plaques in the brain. In a study presented at the Alzheimer’s Association International Conference (AAIC) in London, UK, July 2017, by Nenad Bogdanovic, MD, PhD, of the University of Oslo in Norway, amyloid PET imaging was found to be a fundamental diagnostic tool for AD, establishing a definite diagnosis or excluding AD in all 50 study participants.2 The use of cerebrospinal fluid (CSF) amyloid testing with a higher amyloid-beta plaque threshold than that traditionally used to establish a positive finding also resulted in high diagnostic accuracy, resulting in diagnosis or exclusion in 44 of 50 participants (88%) compared with only 21 individuals (42%) using traditional cutoffs.2

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