Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: 136(1)
Published: Dec. 26, 2024
Language: Английский
Vaccines, Journal Year: 2024, Volume and Issue: 12(9), P. 973 - 973
Published: Aug. 28, 2024
Neurodegenerative diseases (ND) give rise to significant declines in motor, autonomic, behavioral, and cognitive functions. Of these conditions, Alzheimer's disease (AD) Parkinson's (PD) are the most prevalent, impacting over 55 million people worldwide. Given staggering financial toll on global economy their widespread manifestation, NDs represent a critical issue for healthcare systems Current treatment options merely seek provide symptomatic relief or slow rate of functional decline remain financially inaccessible many patients. Indeed, no therapy has yet demonstrated potential halt trajectory NDs, let alone reverse them. It is now recognized that brain accumulation pathological variants AD- PD-associated proteins (i.e., amyloid-β, Tau, α-synuclein) begins years decades before onset clinical symptoms. Accordingly, there an urgent need pursue therapies prevent neurodegenerative processes associated with protein aggregation long diagnosis can be made. These must safe, convenient, affordable ensure broad coverage at-risk populations. Based intervene symptoms appear, this review, we present rationale greater investment support development active immunotherapy prevention two common based safety profile, ability specifically target proteins, as well significantly lower costs manufacturing distribution, which stands expand accessibility millions globally.
Language: Английский
Citations
1
Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 30, 2024
Life expectancy has consistently increased in the world population as a result of significant improvements health systems and life quality, thereby allowing many more people to reach ages where neurodegenerative diseases (NDs) are prevalent.1 Currently, than three billion affected by ND globally, number that continues rise, reflecting not only aging but also exposure environmental risk factors associated with modern lifestyle, such poor diet, sedentarism pollutants.2-4 Since there is no treatment capable preventing initiation and/or progression ND, these conditions high morbidity mortality ratios, significantly contributing global burden disease profoundly impacting public worldwide.2, 4 The WHO emphasizes need reduce this through advancements diagnostic methods targeting early detection, development innovative therapies stopping/slowing prevention strategies.2 In broad terms, encompasses large group heterogenous disorders varying cause, symptom presentation course, Alzheimer's (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS), multiple (MS), among others.5 symptomatology arise from progressive loss neuronal function specific areas central or peripheral nervous system, resulting particular set symptoms (cognitive, sensory motor) primarily main each condition. complex nature NDs, encompassing genetic, epigenetic factors, made it challenging identify critical mechanisms triggering degeneration its progression.5, 6 A deeper understanding basic involved neurodegeneration neuroprotection is, thus, essential biomarkers can allow detection NDs,7, 8 well provide new targets for developing successful pharmacological interventions.9 This special issue was conceptualized address some limitations insights about potential therapeutic strategies NDs. Our collection papers highlights molecular control balance between neurotoxicity neuroprotection, bio-metals dyshomeostasis,10 mitochondrial function,11 oxidative stress12 neuroplasticity regulation.13 It covers advances towards biomarkers,14, 15 drug development11, 16-18 novel approaches.11, 19-23 review Jayant Flora16 on copper's role neurological relates broader context metal dyshomeostasis, which play crucial roles regulating stress, neuroinflammation protein misfolding.24 Based evidence presented, authors propose copper-targeting approaches could improved alternatives particularly AD, discuss safety concerns compounds. Poblano et al.17 reviewed important genetic factor associate AD pathology, APOE4 (Apolipoprotein E4) transport redistribution lipids brain. uniquely emerging allele regulate beta-amyloid aggregation, mimetic peptides, small-molecule correctors HAE-4 antibodies, adding valuable information field. Furthermore, repurposing other drugs, like loop diuretics antidepressants, prevent inhibiting APOE4-catalysed aggregation. prominent lipid mediators pathology further addressed perspectives. Yazdi al.12 focused responsible across cellular membranes, ATP-binding cassette transporter G1 (ABCG1). dysregulation ABCG1 impair homeostasis favour proposing be targeted fight progression. Pereira-Castelo al.22 delve into intricate less-known neurolipids—endocannabinoids, lysophosphatidic acid (LPA) sphingosine-1-phosphate (S1P)—in pathogenesis including PD Huntington's (HD). paper discusses how neurolipids contribute down-regulating increasing synaptic plasticity. light discussed, suggest neurolipid avenues, preclinical studies show promising results cannabinoids S1P modulators animal models. Arjmand al.11 oestrogen, lipid-derived hormone, underscoring participation oestrogen receptors attenuating mitochondrial-related dysfunctions promoting neuroprotection. interest women undergoing hormonal changes rational personalized women, at higher during perimenopause. Moroz al.25 present newer beyond mediators, transient receptor (TRP) channels oxytocin, offering multi-targeted approach slow line perspective, Nishit al.18 detailed TRP influence pathogenesis, regulation calcium homeostasis, excitotoxicity stress. Supported evidence, neuroprotective NDs urge investigation models support future clinical investigations. natural products focusing polyphenols potentially profile. Moreira Vasconcelos al.19 highlight recent scientific findings minor phenolic compounds, eugenol resveratrol, mitigate reducing inflammation abnormalities. By lesser studied encourages research explore their effect PD. described effects phytocannabinoids, representing brain disorders. An vitro study20 describes properties known cannabichromene (CBC), cannabigerol (CBG) cannabinol (CBN), suggesting agents AD. Another study same group21 investigated various medicinal cannabis extracts containing THC CBD against amyloid-beta (Aβ1-42)-induced toxicity, highlighting importance different cannabinoid formulations derived treatment. anti-inflammatory cannabidiol (CBD) phytocannabinoids then collectively discussed,23 action presenting supporting efficacy treating epilepsy, sclerosis, psychiatric treatments slowing progression, Tuominen Renko14 identifying reliable detect prodromal stages, timely neurotrophic therapies. biochemical imaging biomarkers, alpha-synuclein neuroimaging techniques. On hand, Ghosh al.15 methodologies both PD, emphasizing non-invasive biosensors advancing diagnosis, methodologies, artificial intelligence, machine learning approaches. dysregulated dementia observed patients suffering recurrent depressive disorder, considered convergent neurobiological hypothesis underlying comorbidity proposed.26 open possibilities future. integrating compounds advanced biomarker analyses, offers perspectives fostering identification SJ been supported Lundeck Foundation (R366-2021-255), Jasha Fonden Aarhus University Research (AUFF Starting Grant). an affiliated researcher Danish Institute Translational Neuroscience – DANDRITE. There competing interests work. Data sharing applicable article datasets were generated analysed current study.
Language: Английский
Citations
0
Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: 136(1)
Published: Dec. 26, 2024
Language: Английский
Citations
0