Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 1 - 25
Опубликована: Окт. 11, 2024
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(3), С. 188890 - 188890
Опубликована: Март 29, 2023
Язык: Английский
Процитировано
204
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Янв. 1, 2024
Abstract Combining existing drug therapy is essential in developing new therapeutic agents disease prevention and treatment. In preclinical investigations, combined effect of certain known drugs has been well established treating extensive human diseases. Attributed to synergistic effects by targeting various pathways advantages, such as reduced administration dose, decreased toxicity, alleviated resistance, combinatorial treatment now being pursued delivering combat major clinical illnesses, cancer, atherosclerosis, pulmonary hypertension, myocarditis, rheumatoid arthritis, inflammatory bowel disease, metabolic disorders neurodegenerative Combinatorial involves combining or co-delivering two more for a specific disease. Nanoparticle (NP)-mediated delivery systems, i.e., liposomal NPs, polymeric NPs nanocrystals, are great interest wide range due targeted delivery, extended release, higher stability avoid rapid clearance at infected areas. This review summarizes targets diseases, clinically approved combinations the development multifunctional emphasizes strategies based on severe Ultimately, we discuss challenging NP-codelivery translation provide potential approaches address limitations. offers comprehensive overview recent cutting-edge NP-mediated combination
Язык: Английский
Процитировано
112
Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16
Опубликована: Фев. 7, 2023
ATF4 is a cellular stress induced bZIP transcription factor that hallmark effector of the integrated response. The response triggered by phosphorylation alpha subunit eukaryotic initiation 2 complex can be carried out responsive kinases; GCN2, PERK, PKR, and HRI. eIF2α downregulates mRNA translation en masse , however upregulated. output two contradicting outcomes in cells; pro-survival or apoptosis. mechanism for choice between these unknown, combinations heterodimerisation partners post-translational modifications have been linked to this regulation. This semi-systematic review article covers target genes, modifications. Together, aims useful resource elucidate mechanisms controlling effects Additional putative roles protein cell division synaptic plasticity are outlined.
Язык: Английский
Процитировано
98
Translational Neurodegeneration, Год журнала: 2023, Номер 12(1)
Опубликована: Апрель 14, 2023
Abstract Redox homeostasis refers to the balance between production of reactive oxygen species (ROS) as well nitrogen (RNS), and their elimination by antioxidants. It is linked all important cellular activities oxidative stress a result imbalance pro-oxidants antioxidant species. Oxidative perturbs many activities, including processes that maintain integrity DNA. Nucleic acids are highly therefore particularly susceptible damage. The DNA damage response detects repairs these lesions. Efficient repair essential for maintaining viability, but they decline considerably during aging. deficiencies in increasingly described age-related neurodegenerative diseases, such Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis Huntington’s disease. Furthermore, has long been associated with conditions. Moreover, both redox dysregulation increase significantly aging, which biggest risk factor diseases. However, links dysfunction damage, joint contributions pathophysiology conditions, only just emerging. This review will discuss associations address increasing evidence an major source disorders. Understanding connections may facilitate better understanding disease mechanisms, ultimately lead design therapeutic strategies based on preventing
Язык: Английский
Процитировано
64
Neural Regeneration Research, Год журнала: 2023, Номер 19(6), С. 1262 - 1276
Опубликована: Окт. 2, 2023
The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis considered the main pathological hallmarks this devastating disease. Physiologically, these two proteins produced expressed within normal human body. However, under conditions, abnormal expression, post-translational modifications, conformational changes, truncation can make prone aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior various neurological diseases, such as disease, Parkinson's amyotrophic lateral sclerosis, well retinal neurodegenerative diseases like Glaucoma age-related macular degeneration. Additionally, been linked cardiovascular cancer, traumatic brain injury, diabetes, which all leading causes morbidity mortality. In comprehensive review, we provide an overview connections a spectrum disorders.
Язык: Английский
Процитировано
39
Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16
Опубликована: Май 14, 2024
As the global population ages, incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that β-amyloid protein (Aβ) deposition is a key factor leading AD. However, clinical efficacy treating AD anti-Aβ antibodies not satisfactory, suggesting Aβ amyloidosis may be pathological change rather than Identification causes and development corresponding prevention treatment strategies an important goal current research. Following discovery soluble oligomeric forms (AβO) in 1998, scientists began focus on neurotoxicity AβOs. endogenous neurotoxin, active growth AβOs can lead neuronal death, which believed occur before plaque formation, are factors PANoptosis, newly proposed concept cell death includes known modes pyroptosis, apoptosis, necroptosis, form regulated PANoptosome complex. Neuronal survival depends proper mitochondrial function. Under conditions AβO interference, dysfunction occurs, releasing lethal contents as potential upstream effectors PANoptosome. Considering critical role neurons cognitive function well regulatory survival, investigation mechanisms PANoptosis crucial. This review describes disruption elucidates how activate causing during AD, providing guidance for targeted strategies.
Язык: Английский
Процитировано
12
Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)
Опубликована: Март 2, 2024
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, spinal cord. Unfortunately, there are few effective treatments, thus remains critical need to find novel interventions that can mitigate against its effects. Whilst aetiology of ALS unclear, ageing major risk factor. Ageing slowly progressive process marked by functional decline an organism over lifespan. However, it unclear how promotes ALS. At molecular cellular level specific hallmarks characteristic normal ageing. These highly inter-related overlap significantly with each other. Moreover, whilst process, striking similarities at between these factors neurodegeneration Nine were originally proposed: genomic instability, loss telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, proteostasis, mitochondrial dysfunction, stem cell exhaustion, altered inter-cellular communication. recently (2023) expanded include dysregulation autophagy, inflammation dysbiosis. Hence, given latest updates hallmarks, their close association disease processes ALS, new examination relationship pathophysiology warranted. In this review, we describe possible mechanisms which impacts on neurodegenerative implicated therapeutic may arise from this.
Язык: Английский
Процитировано
11
Antioxidants, Год журнала: 2024, Номер 13(10), С. 1208 - 1208
Опубликована: Окт. 8, 2024
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.
Язык: Английский
Процитировано
10
Antioxidants, Год журнала: 2024, Номер 13(12), С. 1462 - 1462
Опубликована: Ноя. 28, 2024
Upregulation of reactive oxygen species (ROS) levels is a principal feature observed in the brains neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s (AD). In these diseases, oxidative stress can disrupt blood–brain barrier (BBB). This disruption allows neurotoxic plasma components, blood cells, pathogens to enter brain, leading increased ROS production, mitochondrial dysfunction, inflammation. Collectively, factors result protein modification, lipid peroxidation, DNA damage, and, ultimately, neural cell damage. this review article, we present mechanisms by which damage leads BBB breakdown brain diseases. Additionally, summarize potential therapeutic approaches aimed at reducing that contributes
Язык: Английский
Процитировано
10
Frontiers in Neuroscience, Год журнала: 2023, Номер 17
Опубликована: Ноя. 16, 2023
Alzheimer’s disease (AD) is the most common form of dementia. AD a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, behavioral changes. Neuropathology hallmarks such as amyloid beta (Aβ) plaques neurofibrillary tangles containing neuron-specific protein tau associated with changes in fluid biomarkers Aβ, phosphorylated (p-tau)-181, p-tau 231, 217, glial fibrillary acidic (GFAP), neurofilament light (NFL). Another pathological feature neural damage hyperactivation astrocytes, that can cause increased pro-inflammatory mediators oxidative stress. In addition, reduced brain glucose metabolism mitochondrial dysfunction appears up to 15 years before onset clinical symptoms. As utilization compromised patients AD, ketone bodies (KBs) may serve an alternative source energy. KBs are generated from β-oxidation fatty acids, which enhanced following consumption ketogenic diets high fat, moderate protein, low carbohydrate. have been shown cross blood barrier improve energy metabolism. This review comprehensively summarizes current literature on how increasing support for first time, this discusses effects diet putative (mainly 181), GFAP, NFL, role neuroinflammation, stress,
Язык: Английский
Процитировано
11