Genetically modified non-human primate models for research on neurodegenerative diseases DOI Open Access

Ming-Tian Pan,

Han Zhang, Xiao‐Jiang Li

и другие.

动物学研究, Год журнала: 2024, Номер 45(2), С. 263 - 274

Опубликована: Янв. 1, 2024

Neurodegenerative diseases (NDs) are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), amyotrophic lateral sclerosis (ALS). Currently, there no therapies available can delay, stop, or reverse the pathological progression NDs in clinical settings. As population ages, imposing huge burden on public health systems affected families. Animal models important tools for preclinical investigations to understand pathogenesis test potential treatments. While numerous rodent have been developed enhance our understanding mechanisms, limited success translating findings from animal practice suggests is still need bridge this translation gap. Old World non-human primates (NHPs), such as rhesus, cynomolgus, vervet monkeys, phylogenetically, physiologically, biochemically, behaviorally most relevant humans. This particularly evident similarity structure function their central nervous systems, rendering species uniquely valuable neuroscience research. Recently, development several genetically modified NHP has successfully recapitulated key pathologies revealed novel mechanisms. review focuses efficacy NHPs modeling insights gained, well challenges associated with generation complexities involved subsequent analysis.

Язык: Английский

Peripheral and central immune system crosstalk in Alzheimer disease — a research prospectus DOI Open Access
Brianne M. Bettcher, Malú G. Tansey, Guillaume Dorothée

и другие.

Nature Reviews Neurology, Год журнала: 2021, Номер 17(11), С. 689 - 701

Опубликована: Сен. 14, 2021

Язык: Английский

Процитировано

293

The interplay between immunosenescence and age-related diseases DOI Open Access
Florencia María Barbé‐Tuana, Giselle A. Funchal, Carine Raquel Richter Schmitz

и другие.

Seminars in Immunopathology, Год журнала: 2020, Номер 42(5), С. 545 - 557

Опубликована: Авг. 3, 2020

Язык: Английский

Процитировано

259

Biological aging processes underlying cognitive decline and neurodegenerative disease DOI Creative Commons
Mitzi M. Gonzales, Valentina R. Garbarino, Erin Pollet

и другие.

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(10)

Опубликована: Май 15, 2022

Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability mortality in later life. As with many chronic conditions, aging is single most influential factor development of ADRD. Even older adults who remain free dementia throughout their lives, cognitive decline neurodegenerative changes appreciable advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview cognition, brain morphology, neuropathological protein accumulation across lifespan humans, complementary mechanistic evidence from animal models. Next, highlight selected processes that differentially regulated disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular inflammation, lipid dysregulation. We summarize research clinical translational studies link biological underlying ADRD pathogenesis. Targeting fundamental may represent a yet relatively unexplored avenue attenuate both age-related Collaboration fields geroscience neuroscience, coupled new models more closely align human processes, necessary advance novel therapeutic discovery realm.

Язык: Английский

Процитировано

198

Emerging Microglia Biology Defines Novel Therapeutic Approaches for Alzheimer’s Disease DOI Creative Commons
Joseph W. Lewcock, Kai Schlepckow, Gilbert Di Paolo

и другие.

Neuron, Год журнала: 2020, Номер 108(5), С. 801 - 821

Опубликована: Окт. 23, 2020

Язык: Английский

Процитировано

180

The neuroimmune axis of Alzheimer’s disease DOI Creative Commons
Mehdi Jorfi,

Anna Maaser-Hecker,

Rudolph E. Tanzi

и другие.

Genome Medicine, Год журнала: 2023, Номер 15(1)

Опубликована: Янв. 26, 2023

Abstract Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder with multifaceted neuropathological features, including β-amyloid plaques, neurofibrillary tangles, neuroinflammation. Over the past decade, emerging evidence has implicated both beneficial pathological roles for innate immune genes cells, peripheral cells such as T which can infiltrate brain either ameliorate or exacerbate AD neuropathogenesis. These findings support neuroimmune axis of AD, in interplay adaptive systems inside outside critically impacts etiology pathogenesis AD. In this review, we discuss complexities neuropathology at levels genetics cellular physiology, highlighting signaling pathways associated risk interactions among brain. We emphasize role mechanisms by monocytes, influence neuropathology, microglial clearance amyloid-β peptide, key component plaque cores, pro-inflammatory cytotoxic activity microglia, astrogliosis, their vasculature. Finally, review challenges outlook establishing immune-based therapies treating preventing

Язык: Английский

Процитировано

174

Targeting microglial autophagic degradation in NLRP3 inflammasome-mediated neurodegenerative diseases DOI
Anguo Wu, Xiaogang Zhou, Gan Qiao

и другие.

Ageing Research Reviews, Год журнала: 2020, Номер 65, С. 101202 - 101202

Опубликована: Ноя. 5, 2020

Язык: Английский

Процитировано

159

Multifunctional nanoparticle-mediated combining therapy for human diseases DOI Creative Commons
Xiaotong Li,

Xiuju Peng,

Makhloufi Zoulikha

и другие.

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

148

Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity DOI Creative Commons
Simone Bido, Sharon Muggeo, Luca Massimino

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Окт. 29, 2021

Abstract Recent findings in human samples and animal models support the involvement of inflammation development Parkinson’s disease. Nevertheless, it is currently unknown whether microglial activation constitutes a primary event neurodegeneration. We generated new mouse model by lentiviral-mediated selective α-synuclein (αSYN) accumulation cells. Surprisingly, these mice developed progressive degeneration dopaminergic (DA) neurons without endogenous αSYN aggregation. Transcriptomics functional assessment revealed that αSYN-accumulating cells strong reactive state with phagocytic exhaustion excessive production oxidative proinflammatory molecules. This inflammatory created molecular feed-forward vicious cycle between microglia IFNγ-secreting immune infiltrating brain parenchyma. Pharmacological inhibition nitrosative molecule was sufficient to attenuate These results suggest induces DA neuronal promoting exhaustion, an excessively toxic environment recruitment peripheral

Язык: Английский

Процитировано

125

Mitochondrial function in development and disease DOI Creative Commons
Marlies P. Rossmann, Sonia M. Dubois, Suneet Agarwal

и другие.

Disease Models & Mechanisms, Год журнала: 2021, Номер 14(6)

Опубликована: Июнь 1, 2021

Mitochondria are organelles with vital functions in almost all eukaryotic cells. Often described as the cellular 'powerhouses' due to their essential role aerobic oxidative phosphorylation, mitochondria perform many other beyond energy production. As signaling organelles, communicate nucleus and help maintain homeostasis, allow adaptation diverse stresses, steer cell fate decisions during development. have taken center stage research of normal pathological processes, including tissue homeostasis metabolism, neurodegeneration, immunity infectious diseases. The central that assume within cells is evidenced by broad impact mitochondrial diseases, caused defects either or nuclear genes encoding for proteins, on different organ systems. In this Review, we will provide reader a foundation 'hardware', mitochondrion itself, its specific dynamics, quality control mechanisms cross-organelle communication, roles driver an innate immune response, focus development, disease aging. We further discuss how DNA inherited, mutation affects organismal fitness, current therapeutic approaches diseases both model organisms humans.

Язык: Английский

Процитировано

107

Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials DOI Creative Commons
Jifei Miao,

Haixia Ma,

Yang Yang

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Июнь 15, 2023

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregation in the brain. Recent studies have revealed critical role of microglia AD pathogenesis. This review provides comprehensive summary current understanding microglial involvement AD, focusing on genetic determinants, phenotypic state, phagocytic capacity, neuroinflammatory response, and impact synaptic plasticity neuronal regulation. Furthermore, recent developments drug discovery targeting are reviewed, highlighting potential avenues for therapeutic intervention. emphasizes essential insights into treatments.

Язык: Английский

Процитировано

98