Molecular Neurobiology, Год журнала: 2023, Номер 60(12), С. 6852 - 6868
Опубликована: Июль 28, 2023
Язык: Английский
Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115218 - 115218
Опубликована: Июль 29, 2023
Alzheimer's disease (AD) is the most common neurodegenerative disease, resulting in loss of cognitive ability and memory. However, there no specific treatment to mechanistically inhibit progression drugs only provide symptom relief do not fundamentally reverse AD. Current studies show that triggering receptor expressed on myeloid cells 2 (TREM2) predominantly microglia central nervous system (CNS) involved proliferation, survival, migration phagocytosis. The current academic view suggests TREM2 its ligands have CNS protective effects Specifically, acts by regulating function promoting clearance neuronal toxic substances abnormal proteins microglia. In addition, also inflammatory response cell signaling pathways, affecting immune regulatory role Although relationship between has been extensively studied, mechanism action fully understood. purpose this review a comprehensive analysis research TREM2, including regulation response, lipid metabolism phagocytosis AD, explore potential application prospects as well limitations targeting for
Язык: Английский
Процитировано
43
Movement Disorders, Год журнала: 2020, Номер 36(5), С. 1070 - 1085
Опубликована: Ноя. 21, 2020
ABSTRACT Parkinson's disease (PD) is a progressive neurodegenerative where dopaminergic neurons in the substantia nigra are lost, resulting decrease striatal dopamine and, consequently, motor control. Dopaminergic degeneration associated with appearance of Lewy bodies, which contain membrane structures and proteins, including α‐synuclein (α‐Syn), surviving neurons. PD displays multifactorial pathology develops from interactions between multiple elements, such as age, environmental conditions, genetics. Mutations GBA1 gene represent one major genetic risk factors for PD. This encodes an essential lysosomal enzyme called β‐glucocerebrosidase (GCase), responsible degrading glycolipid glucocerebroside into glucose ceramide. GCase can generate glucosylated cholesterol via transglucosylation also degrade sterol glucoside. Although molecular mechanisms that predispose individual to neurodegeneration remain unknown, role deserves consideration. Disturbed cellular metabolism, reflected by accumulation ‐associated models, could contribute changes lipid rafts, necessary synaptic localization vesicle cycling modulation integrity. α‐Syn has been implicated regulation neuronal cholesterol, facilitates oligomers. In this review, we integrate results previous studies describe landscape homeostasis function. We discuss its implication body pathophysiological underlying PD, focusing on cholesterol. © 2020 The Authors. Movement Disorders published Wiley Periodicals LLC behalf International Parkinson Disorder Society
Язык: Английский
Процитировано
87
Frontiers in Neuroscience, Год журнала: 2019, Номер 13
Опубликована: Май 31, 2019
In Alzheimer's disease (AD), both cholesterol and glucose dysmetabolism precede the onset of memory deficit contribute to progression. It is indeed now believed that oxidized in form oxysterols altered uptake are main triggers AD affecting production clearance Aβ, tau phosphorylation. However, only a few studies highlight relationship between them, suggesting importance further extensive on this topic. Recently, molecular link was demonstrated oxidative metabolism brain. particular, 27-hydroxycholesterol, key linker hypercholesterolemia increased risk, considered biomarker for reduced metabolism. fact, its excess increases activity renin-angiotensin system brain, thus reducing insulin-mediated uptake, which has major impact brain functioning. Despite important evidence regarding role oxysterol regulating by neurons, involvement other oxidation products have been clearly be players AD, cannot ruled out. This review highlights current understanding potential progression, bidirectional crosstalk these two phenomena.
Язык: Английский
Процитировано
67
Antioxidants, Год журнала: 2021, Номер 10(5), С. 740 - 740
Опубликована: Май 7, 2021
The development of Alzheimer’s disease (AD) is influenced by several events, among which the dysregulation cholesterol metabolism in brain plays a major role. Maintenance homeostasis essential for neuronal functioning and development. To maintain steady-state level, excess converted into more hydrophilic metabolite 24-S-hydroxycholesterol (24-OHC), also called cerebrosterol, neuron-specific enzyme CYP46A1. A growing bulk evidence suggests that oxidation products, named oxysterols, are link connecting altered to AD. It has been shown levels some including 27-hydroxycholesterol, 7β-hydroxycholesterol 7-ketocholesterol, significantly increase AD brains contributing progression. In contrast, 24-OHC decrease, likely due loss. Among different certainly one whose role most controversial. dominant oxysterol shows it represents signaling molecule great importance function. However, numerous studies highlighted potential favoring development, since promotes neuroinflammation, amyloid β (Aβ) peptide production, oxidative stress cell death. parallel, exert beneficial effects against progression, such as preventing tau hyperphosphorylation Aβ production. this review we focus on current knowledge controversial pathogenesis, reporting detailed overview findings about its biological samples noxious or neuroprotective brain. Given relevant pathophysiology, targeting could be useful prevention slowing down
Язык: Английский
Процитировано
53
Acta Neuropathologica Communications, Год журнала: 2022, Номер 10(1)
Опубликована: Март 16, 2022
Previous studies show that 3β-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In cholesterol synthetic metabolism, DHCR24 is known as heavily key synthetase synthesis. Moreover, mutations gene result inhibition enzymatic activity DHCR24, causing deficiency and desmosterol accumulation. Furthermore, vitro also demonstrated knockdown lead to synthesis, decrease plasma membrane intracellular level. Obviously, could play crucial role maintaining homeostasis via control Over past two decades, accumulating data suggests downregulated by major risk factors for AD, suggesting potential link between downregulation pathogenesis. Thus, loss seems be induced possible causative AD. According previous our study, we further found reduced level compartments obviously was involved β-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal lipid raft disorganization are linked neuropathological impairments which associated with Therefore, based on research suppose deficiency/loss might pathogenesis
Язык: Английский
Процитировано
33
Frontiers in Neuroscience, Год журнала: 2023, Номер 17
Опубликована: Март 7, 2023
Alzheimer’s disease (AD) is the most common neurodegenerative disease. There are many studies targeting extracellular deposits of amyloid β-peptide (Aβ) and intracellular neurofibrillary tangles (NFTs), however, there no effective treatments to halt progression. Mitochondria-associated endoplasmic reticulum membranes (MAMs) have long been found be associated with various pathogenesis hypotheses AD, such as Aβ deposition, mitochondrial dysfunction, calcium homeostasis. However, a lack literature summarizing recent advances in mechanism treatment studies. Accordingly, this article reviews latest research involving roles MAM structure tethering proteins AD summarizes potential strategies MAMs dissect perspectives for AD.
Язык: Английский
Процитировано
16
International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(5), С. 1046 - 1046
Опубликована: Фев. 28, 2019
A present review is devoted to the analysis of literature data and results own research. Skeletal muscle neuromuscular junction specialized trigger striated fiber contraction in response motor neuron activity. The safety factor at strongly depends on a variety pre- postsynaptic factors. focuses crucial role membrane cholesterol maintain high efficiency transmission. Cholesterol metabolism junction, its synaptic vesicle cycle neurotransmitter release, endplate electrogenesis, as well contribution synaptogenesis, integrity, disorders are discussed.
Язык: Английский
Процитировано
53
Biochimie, Год журнала: 2018, Номер 153, С. 80 - 85
Опубликована: Май 4, 2018
Язык: Английский
Процитировано
49
Frontiers in Neuroscience, Год журнала: 2019, Номер 13
Опубликована: Дек. 13, 2019
The aggregation of the human tau protein into neurofibrillary tangles is directly diagnostic many neurodegenerative conditions termed tauopathies. species, factors and events that are responsible for initiation propagation not clearly established, even in a simplified artificial vitro system. This motivates mechanistic study recombinant from soluble to fibrillar forms, which polyanionic cofactors most commonly used external inducer. In this study, we performed biophysical characterizations unravel mechanisms by induce fibrillization. We first reinforce idea limiting factor generate ThT-active fibrils, establish they act as templating reactant trigger conformational rearrangement. show heparin has superior potency recruiting monomeric aggregation-competent species compared any constituent intermediate or aggregate "seeds." form complexes whose evolution toward fibrils tightly regulated tau-cofactor interactions. Remarkably, it possible find mild complex with without forming except when an catalyst (e.g., seed) provided overcome energy barrier. cellular context, propose could associate metastable remains "inert" reversible, until encountering relevant seed can irreversible transition β-sheet containing species.
Язык: Английский
Процитировано
46
Critical Reviews in Food Science and Nutrition, Год журнала: 2021, Номер 62(13), С. 3613 - 3630
Опубликована: Янв. 5, 2021
Phytosterols and their oxidation products, namely oxyphytosterols, are natural compounds present in plant foods. With increased intake of phytosterol-enriched functional food the exposure both phytosterols oxyphytosterols is rising. Over past ten years, researches have been focused on absorption metabolism human body, as well biological effects. More importantly, recent studies showed that can traverse blood-brain barrier accumulate brain. As brain health problems resulting from ageing being more serious, attenuating central nervous system (CNS) disorders with active becoming a hot topic. shown to implicated cognition altering pathologies several CNS disorders, including Alzheimer's disease multiple sclerosis. We will overview these findings focus contents dietary intake, origins brain, illustrate molecular pathways through which they affect health, terms inflammation, cholesterol homeostasis, oxidative stress, mitochondria function. The existing scientific gaps knowledge also discussed, highlighting research directions future.
Язык: Английский
Процитировано
33