Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 3 - 27
Published: Nov. 29, 2024
Language: Английский
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1113 - 1113
Published: Jan. 17, 2024
Mucopolysaccharidoses (MPSs) are a group of inborn errors the metabolism caused by deficiency in lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time various tissues and disrupt multiple biological systems, including catabolism other substances, autophagy, mitochondrial function. pathological changes ultimately increase oxidative stress activate innate immunity inflammation. We have described pathophysiology MPS activated inflammation this paper, starting with accumulating primary storage materials, GAGs. At initial stage GAG accumulation, affected tissues/cells reversibly but progress irreversibly to: (1) disruption substrate degradation pathogenic function, (2) cellular dysfunction, secondary/tertiary accumulation (toxins such as GM2 or GM3 ganglioside, etc.), inflammatory process, (3) progressive tissue/organ damage cell death (e.g., skeletal dysplasia, CNS impairment, etc.). For current future treatment, several potential treatments for that can penetrate blood–brain barrier bone been proposed and/or clinical trials, targeting peptides molecular Trojan horses monoclonal antibodies attached via receptor-mediated transport. Gene therapy trials AAV, ex vivo LV, Sleeping Beauty transposon system underway innovative therapeutic options. In addition, possible immunomodulatory reagents suppress symptoms summarized review.
Language: Английский
Citations
8
Neuropharmacology, Journal Year: 2025, Volume and Issue: 269, P. 110346 - 110346
Published: Feb. 4, 2025
Language: Английский
Citations
1
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: April 8, 2025
Chronic inflammation is an important component of many diseases, including autoimmune intracellular infections, dysbiosis and degenerative diseases. An element this state the mainly positive feedback between inflammatory cytokines, reactive oxygen species (ROS), nitric oxide (NO), increased calcium, hypoxia-inducible factor 1-alpha (HIF-1α) stabilisation mitochondrial oxidative stress, which, under normal conditions, enhance response against pathogens. Autophagy nuclear erythroid 2-related 2 (Nrf2)-mediated antioxidant are negatively coupled with above-mentioned elements to maintain defence at a level appropriate severity infection. The current review first attempt build multidimensional model cellular self-regulation chronic inflammation. It describes feedbacks involved in explains possible pathways by which becomes chronic. multiplicity suggests that symptomatic treatment should focus on inhibiting multiple effectively suppress all dysregulated inflammation, calcium mito-stress other metabolic disturbances.
Language: Английский
Citations
1
Neuropharmacology, Journal Year: 2023, Volume and Issue: 237, P. 109636 - 109636
Published: June 15, 2023
It is now generally accepted that astrocytes are active players in synaptic transmission, so a neurocentric perspective of the integrative signal communication central nervous system shifting towards neuro-astrocentric perspective. Astrocytes respond to activity, release chemical signals (gliotransmitters) and express neurotransmitter receptors (G protein-coupled ionotropic receptors), thus behaving as co-actors with neurons system. The ability G physically interact through heteromerization, forming heteromers receptor mosaics new distinct recognition transduction pathways, has been intensively studied at neuronal plasma membrane, changed view One best-known examples receptor-receptor interaction relevant consequences for both physiological pharmacological points view, given by adenosine A2A dopamine D2 on membrane striatal neurons. Here we review evidence native can heteromerization well. Astrocytic A2A-D2 were found able control glutamate from astrocyte processes. processes discussed far their potential relevance glutamatergic transmission striatum concerned, including roles dysregulation pathological conditions schizophrenia or Parkinson's disease.
Language: Английский
Citations
17
IBRO Neuroscience Reports, Journal Year: 2023, Volume and Issue: 14, P. 210 - 234
Published: Feb. 10, 2023
Some of the greatest challenges in medicine are neurodegenerative diseases (NDs), which remain without a cure and mostly progress to death. A companion study employed toolkit methodology document 2001 plant species with ethnomedicinal uses for alleviating pathologies relevant NDs, focusing on its relevance Alzheimer's disease (AD). This aimed find plants therapeutic bioactivities range NDs. 1339 were found have bioactivity from literature NDs such as Parkinson's disease, Huntington's AD, motor neurone diseases, multiple sclerosis, prion Neimann-Pick glaucoma, Friedreich's ataxia Batten disease. 43 types found, reducing protein misfolding, neuroinflammation, oxidative stress cell death, promoting neurogenesis, mitochondrial biogenesis, autophagy, longevity, anti-microbial activity. Ethno-led selection was more effective than random species. Our findings indicate that provide large resource ND potential. The extensive validate usefulness mining this data. We number documented able modulate molecular mechanisms underlying various key pathologies, revealing promising even profound capacity halt reverse processes neurodegeneration.
Language: Английский
Citations
16
European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116117 - 116117
Published: Jan. 23, 2024
Language: Английский
Citations
7
Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14
Published: Feb. 27, 2023
Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM 2.5 ), including combustion and friction ultrafine PM (UFPM) industrial nanoparticles (NPs) starting in utero , are linked early pediatric young adulthood aberrant neural protein accumulation, hyperphosphorylated tau (p-tau), beta-amyloid (Aβ 1 − 42 α-synuclein (α syn) TAR DNA-binding 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic natural sources NPs enter the brain through nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, placental barriers. On a global scale, most important outdoor motor traffic emissions. This study focuses on neuropathology heterogeneity overlap AD, PD, FTLD, ALS older adults, their similarities with young, highly exposed urbanites, strong link sleep disorders. Critical information includes how this cross all biological barriers, interact soluble proteins key organelles, result oxidative, endoplasmic reticulum, mitochondrial stress, neuroinflammation, DNA damage, aggregation misfolding, faulty complex quality control. The toxicity makes them powerful candidates for development progression fatal common neurodegenerative diseases, having disturbances. A detailed residential history, proximity high-traffic roads, occupational histories, high-emission (i.e., factories, burning pits, forest fires, airports), indoor (tobacco, wood winter, cooking fumes, microplastics house dust), consumption NPs, along neurocognitive neuropsychiatric critical. Environmental pollution is ubiquitous, early, cumulative risk factor neurodegeneration Prevention deadly neurological diseases associated air should be public health priority.
Language: Английский
Citations
15
Brain Research Bulletin, Journal Year: 2023, Volume and Issue: 199, P. 110668 - 110668
Published: May 15, 2023
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Inflammation has been observed in both idiopathic and familial forms of PD. Importantly, PD reported more often men than women, having at least 1.5- fold higher risk to develop women. This review summarizes impact biological sex hormones on neuroimmune contributions its investigation animal models Innate peripheral immune systems participate brain neuroinflammation patients reproduced neurotoxin, genetic α-synuclein based Microglia astrocytes are main cells innate system central nervous first react restore homeostasis brain. Analysis serum immunoprofiles female male control show that a great proportion these markers differ between males females. The relationship cerebrospinal fluid inflammatory clinical characteristics or biomarkers shows differences. Conversely, PD, differences inflammation well documented beneficial effects endogenous exogenous estrogenic modulation have reported. Targeting an emerging therapeutic option but gonadal drugs not yet investigated this respect, thus offering new opportunities for specific treatments.
Language: Английский
Citations
12
Life, Journal Year: 2024, Volume and Issue: 14(7), P. 839 - 839
Published: July 1, 2024
Background: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and vivo models to investigate effect Donepezil—an acetylcholinesterase (AChE) inhibitor—on acute period following injury, while focusing on neuroinflammation autophagy- mitophagy-related markers. Methods: The purpose study was potential neuroprotective effects TBI-induced cells donepezil treatment, study, therapeutic by analyzing TBI model involved injuring SH-SY5Y using a cell-injury controller then investigating at concentration 80 μM. made stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers functions were compared 7 days treatment (1 mg/kg/day). Mice divided into four groups: sham operation with saline (18 mice each group). Donepezil administered within 4 h post-TBI. Results: In vitro, found lead increased cell viability 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2′-7′-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. mRNA protein expressions (Cyclooxygenase-2, COX-2; NOD-like receptor 3, NLRP3; Caspase-1; Interleukin-1 beta, IL-1β), as well (death-associated kinase 1, DAPK1; PTEN-induced PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated 1A/1B-light chain 3B (LC3B); Sequestosome-1; p62) all decrease also showed that resulted levels cortical tissue losses swelling group without shown Western blotting markers, especially COX-2 BNIP3L, which most significant decreases. Moreover, an escape latency, alteration rate, improved preference index, altogether pointing better performance Conclusions: may be beneficial improving early phase ameliorating neuroinflammation, autophagy mitophagy.
Language: Английский
Citations
4
Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107578 - 107578
Published: Jan. 5, 2025
Ginseng has been commonly used as a traditional Chinese medicine in Asian countries for thousands of years. Ginsenosides are the main pharmacologically active ingredients isolated from ginseng and have neuroprotective effects treatment neurodegenerative disorders, such Parkinson's disease (PD) Alzheimer's (AD). To summarise investigate protective roles ginsenosides their underlying mechanisms PD AD, we ''Ginsenoside", ''Parkinson's disease", ''Alzheimer's ''anti-inflammatory", ''antioxidant", ''apoptosis" keywords to search extract relevant literature information scientific databases Elsevier, PubMed, Google Scholar databases. In particular, network pharmacology identify potential targets Rg1 Rb1 AD. By analysing existing research advances results, found that ginsenosides, primarily mediated through anti-inflammation, anti-apoptosis anti-oxidative stress, etc, may be associated with PI3K/Akt, BDNF/TrkB, MAPKs, NF-κB, Nrf2 Wnt/β-catenin signalling pathways. This review systematically summarises different Rg1, Rb1, rare AD provides new strategies disorders. Network paradigm using Rb1.
Language: Английский
Citations
0