Knee osteoarthritis accelerates amyloid beta deposition and neurodegeneration in a mouse model of Alzheimer’s disease DOI Creative Commons

Deepak Prasad Gupta,

Young‐Sun Lee, Youngshik Choe

et al.

Molecular Brain, Journal Year: 2023, Volume and Issue: 16(1)

Published: Jan. 2, 2023

Abstract Knee osteoarthritis (OA) is characterized by knee cartilage degeneration and secondary bone hyperplasia, resulting in pain, stiffness, gait disturbance. The relationship between OA neurodegenerative diseases still unclear. This study used an Alzheimer’s disease (AD) mouse model to observe whether accelerates dementia progression analyzing brain histology neuroinflammation. was induced destabilizing the medial meniscus (DMM) control (WT) AD (5xFAD) mice before pathological symptoms. Mouse joints were scanned with a micro-CT scanner. A sham operation as control. Motor cognitive abilities tested after induction. Neurodegeneration, β-amyloid plaque formation, neuroinflammation analyzed immunostaining, Western blotting, RT-PCR tissues. Compared controls, increased inflammatory cytokine levels Furthermore, significantly deposition neuronal loss compared controls. In conclusion, accelerated amyloid neurodegeneration AD-OA mice, suggesting that risk factor for AD.

Language: Английский

Inflammation in obesity, diabetes, and related disorders DOI Creative Commons
Theresa V. Rohm, Daniel T. Meier, Jerrold M. Olefsky

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(1), P. 31 - 55

Published: Jan. 1, 2022

Language: Английский

Citations

1161
Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease DOI
Periyanaina Kesika, Natarajan Suganthy, Bhagavathi Sundaram Sivamaruthi

et al.

Life Sciences, Journal Year: 2020, Volume and Issue: 264, P. 118627 - 118627

Published: Oct. 22, 2020

Language: Английский

Citations

365
ReMAPping the microtubule landscape: How phosphorylation dictates the activities of microtubule‐associated proteins DOI Open Access
Amrita Ramkumar,

Brigette Y Jong,

Kassandra M Ori-McKenney

et al.

Developmental Dynamics, Journal Year: 2017, Volume and Issue: 247(1), P. 138 - 155

Published: Oct. 5, 2017

Classical microtubule‐associated proteins (MAPs) were originally identified based on their co‐purification with microtubules assembled from mammalian brain lysate. They have since been found to perform a range of functions involved in regulating the dynamics microtubule cytoskeleton. Most these MAPs play integral roles organization during neuronal development, remodeling activity, and stabilization maintenance. As result, mutations contribute neurodevelopmental disorders, psychiatric conditions, neurodegenerative diseases. are post‐translationally regulated by phosphorylation depending developmental time point cellular context. Phosphorylation can affect affinity, localization, or overall function particular MAP thus profound implications for health. Here we review MAP1, MAP2, MAP4, MAP6, MAP7, MAP9, tau, DCX, how each is physiology disease. Developmental Dynamics 247:138–155, 2018 . © 2017 Wiley Periodicals, Inc.

Language: Английский

Citations

172
Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer’s Disease Pathogenesis DOI Creative Commons
Anushka Chakravorty,

Cuckoo Teresa Jetto,

Ravi Manjithaya

et al.

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: Nov. 20, 2019

Neurons are highly specialized postmitotic cells that inherently dependent on mitochondria owing to their high bioenergetic demand. Mitochondrial dysfunction is therefore associated with various age-related neurodegenerative disorders such as Alzheimer's disease (AD), wherein accumulation of damaged and dysfunctional has been reported early symptoms further contributing progression. In AD, impairment mitochondrial function causes deficiency, intracellular calcium imbalance oxidative stress thereby aggravating the effect Aβ tau pathologies, leading synaptic dysfunction, cognitive memory loss. Although there reports suggesting intricate parallelism between AD pathologies A aggregation hyperphosphorylated accumulation, factors drive pathogenesis either unclear. addition, emerging evidence suggests quality control (QC) mechanisms mitophagy impaired in AD. As an important QC mechanism, plays a critical role maintaining neuronal health function. Studies show different proteins involved mitophagy, dynamics biogenesis affected The compromised may also be attributed autophagosome-lysosome fusion defects lysosomal acidification. Therapeutic interventions aiming restore functions can used strategy for ameliorating pathogenesis. Recent implicates microglial activation via induction reducing amyloid plaque load. This review summarizes current developments field

Language: Английский

Citations

162
Role of natural products for the treatment of Alzheimer's disease DOI

Tayebeh Noori,

Ahmad Reza Dehpour, Antoni Sureda

et al.

European Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 898, P. 173974 - 173974

Published: Feb. 27, 2021

Language: Английский

Citations

121
The Role of BDNF as a Biomarker in Cognitive and Sensory Neurodegeneration DOI Open Access
Anna Pisani, Fabiola Paciello, V. Del Vecchio

et al.

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(4), P. 652 - 652

Published: April 10, 2023

Brain-derived neurotrophic factor (BDNF) has a crucial function in the central nervous system and sensory structures including olfactory auditory systems. Many studies have highlighted protective effects of BDNF brain, showing how it can promote neuronal growth survival modulate synaptic plasticity. On other hand, conflicting data about expression functions cochlear been reported. Several clinical experimental research showed alterations levels neurodegenerative diseases affecting peripheral system, suggesting that be promising biomarker most conditions, Alzheimer’s disease, shearing loss, or impairment. Here, we summarize current concerning brain domains (olfaction hearing), focusing on BDNF/TrkB signalling pathway activation both physiological pathological conditions. Finally, review significant highlighting possibility to target as early diagnosis cognitive neurodegeneration, opening new opportunities develop effective therapeutic strategies aimed counteract neurodegeneration.

Language: Английский

Citations

49
The genetic landscape of Alzheimer disease DOI
Susana Carmona, John Hardy, Rita Guerreiro

et al.

Handbook of clinical neurology, Journal Year: 2018, Volume and Issue: unknown, P. 395 - 408

Published: Jan. 1, 2018

Language: Английский

Citations

100
Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells DOI Open Access
Ying‐Chieh Wu, Tuuli-Maria Sonninen, Sanni Peltonen

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7710 - 7710

Published: July 19, 2021

The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to brain through active passive transport prevents neurotoxins from entering brain. It also has a clearance function removes carbon dioxide toxic metabolites central nervous system (CNS). Several drugs are unable cross BBB enter CNS, adding complexity drug screens targeting disorders. A well-functioning is essential for maintaining healthy tissue, malfunction BBB, linked its permeability, results in toxins immune cells CNS. This impairment associated with variety neurological diseases, including Alzheimer's disease Parkinson's disease. Here, we summarize current knowledge about neurodegenerative diseases. Furthermore, focus on recent progress using human-induced pluripotent stem cell (iPSC)-derived models study BBB. We review potential novel cell-based platforms modeling address advances key challenges technology human Finally, highlight future directions this area.

Language: Английский

Citations

69
Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets DOI Creative Commons
Zdeněk Fišar

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1676 - 1676

Published: Nov. 11, 2022

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, synaptic nonsynaptic plasticity the lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury synapses neurons accumulation extracellular amyloid plaques intracellular neurofibrillary tangles are considered main morphological neuropathological features AD. Age, genetic epigenetic factors, environmental stressors, lifestyle contribute risk AD onset progression. These factors associated with structural functional changes brain, leading cognitive decline. Biomarkers reflect cause specific function, especially pathways neurotransmission, neuroinflammation, bioenergetics, apoptosis, oxidative nitrosative stress. Even initial stages, is Aβ neurotoxicity, mitochondrial dysfunction, tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that primary neurotoxicity oligomers oligomers, their mutual synergy. For development new efficient drugs, targeting elimination potentiation effects, unwanted protein interactions biomarkers (mainly dysfunction) early stage seems promising.

Language: Английский

Citations

53
Current Pharmacotherapy and Multi-Target Approaches for Alzheimer’s Disease DOI Creative Commons
Siew Lee Cheong,

Jian Kai Tiew,

Yi Hang Fong

et al.

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(12), P. 1560 - 1560

Published: Dec. 14, 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by decreased synaptic transmission and cerebral atrophy with appearance of amyloid plaques neurofibrillary tangles. Cognitive, functional, behavioral alterations are commonly associated the disease. Different pathophysiological pathways AD have been proposed, some which interact influence one another. Current treatment for mainly involves use therapeutic agents to alleviate symptoms in patients. The conventional single-target approaches do not often cause desired effect due its multifactorial origin. Thus, multi-target strategies since undertaken, aim simultaneously target multiple targets involved development AD. In this review, we provide an overview pathogenesis current drug therapies Additionally, rationales examples drugs pharmacological actions against also discussed.

Language: Английский

Citations

46