Browsing by Subject "Neurodegenerative diseases"
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- PublicationOpen AccessEffects of air pollution on dementia over Europe for present and future climate change scenarios(Elsevier, 2022-03) Guzmán, Patricia; Tarín Carrasco, Patricia; Morales-Suárez-Varela, María; Jiménez Guerrero, Pedro; FísicaThe scientific literature is scarce when referring to the influence of atmospheric pollutants on neurodegenerative diseases for present and future climate change scenarios. In this sense, this contribution evaluates the incidence of dementia (Alzheimer's disease, AD, and dementia from unspecified cause, DU) occurring in Europe associated with the exposure to air pollution (essentially NO2 and PM2.5) for the present climatic period (1991–2010) and for a future climate change scenario (RCP8.5, 2031–2050). The GEMM methodology has been applied to air pollution simulations using the chemistry/climate regional model WRF-Chem. Present population data were obtained from NASA's Center for Socioeconomic Data and Applications (SEDAC); while future population projections for the year 2050 were derived from the United Nations (UN) Department of Economic and Social Affairs-Population Dynamics. Overall, the estimated incidence rate (cases per year) of AD and DU associated with exposure to air pollution over Europe is 498,000 [95% confidence interval (95% CI) 348,600–647,400] and 314,000 (95% CI 257,500-401,900), respectively. An important increase in the future incidence rate is projected (around 72% for both types of dementia) when considering the effect of climate change together with the foreseen changes in the future population, because of the expected aging of European population. The climate penalty (impacts of future climate change alone on air quality) has a limited effect on the total changes of dementia (approx. 0.5%), because the large increase in the incidence rate over southern Europe is offset by its decrease over more northern countries, favored by an improvement of air pollution caused by the projected enhancement of rainfall.
- PublicationOpen AccessGene therapy strategies in neurodegenerative diseases(Murcia : F. Hernández, 2001) Giménez y Ribotta, M.Treatment of neurodegenerative diseases by classical pharmacotherapy is restricted by blood-brain barrier which prevents access to the brain of potentially therapeutic molecules. Recent progress in the knowledge of pathophysiological molecular processes, and in the development of molecular biotechnology have opened the way to new therapeutic interventions for these disorders. This chapter reviews the most recent gene therapy strategies using experimental models for neurodegenerative diseases.
- PublicationOpen AccessIntranasal administration: a potential solution for cross-BBB delivering neurotrophic factors(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Zhu, Juehua; Jiang, Yongjun; Xu, Gelin; Liu, XinfengNeurotrophic factors (NTFs) are endogenous polypeptides that regulate the growth, survival, differentiation, and functioning of neurons. The neuroprotective effects of NTFs in experimental animals give strong rationale for developing therapies for neurological disorders. However, when NTFs are applied in clinical trials, great expectation leads to equal disappointment. NTFs are large molecular-weighted and hydrophilic proteins, which limits their access to the central nervous system (CNS) after systemic administration, principally due to poor blood-brain barrier (BBB) permeability and unfavorable pharmacokinetic profiles. Although intracerebral infusion may transport NTFs into the CNS, the invasiveness limits its clinical application. Intranasal administration has been under research for decades and presents promising outcomes in preclinical studies for brain delivering of NTFs. After intranasal delivery, NTFs gain direct and quick access into the CNS at concentrations high enough to elicit their biological effects, bypassing the BBB and minimizing systemic exposure. Due to its invasiveness and convenience, intranasal delivery is feasible for NTFs administration. Although direct evidence of nose-to-brain pathway in human is lacking due to ethical problems, the existence of the nose-to-cerebral spinal fluid pathway has been verified in men. Furthermore, there is abundant indirect evidence for the nose-to-brain pathway as determined by the efficacy of intranasally administered neuroproteins, such as insulin, oxytocin, and vasopressin in clinical trials. Based on the solid preclinical research supporting the efficacy of intranasal NTFs, and the successful clinical application of neuroproteins (not NTFs), it is time to evaluate clinical application of NTFs in treating both acute and chronic CNS diseases
- PublicationOpen AccessMdivi-1: a promising drug and its underlying mechanisms in the treatment of neurodegenerative diseases(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Liu, Xiaoqin; Song, Lijuan; Yu, Jiezhong; Huang, Fang; Li, Yanhua; Ma, CungenMitochondria are energy-producing organelles, and neurons are high energy consumption cells. Therefore, mitochondrial dysfunction is a critical factor in neurodegenerative processes. Mitochondrial division inhibitor-1 (Mdivi-1) is a small chemical inhibitor of mitochondrial division dynamin, which plays multiple roles in mitochondrial dynamics, mitochondrial autophagy, ATP production, the immune response, and Ca2+ homeostasis. Mdivi-1 inhibition of excessive mitochondrial fission exerted cytoprotective effects in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Mdivi-1 changed the mRNA expression of the electron transport chain (ETC) and reduced Ca2+ overload against neuronal injury. Elucidation of the molecular mechanism of Mdivi-1 in neurodegenerative diseases will help evaluate its therapeutic potential and promote its application in clinical studies. The present article focused on the multiple effects of Mdivi-1 on mitochondrial function and its potential therapeutic effects in neurodegenerative diseases.