The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the...The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma.展开更多
Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic mutations.Traditionally,research focused on the impact of genomic mosaicism on clinical phenotype—motivate...Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic mutations.Traditionally,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth syndromes.More recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental exposures.Here,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and homeostasis.Although the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our knowledge.We will provide current definitions and an overview of contemporary detection approaches for genomic mosaicism.Finally,we will discuss the impact and utility of genomic mosaicism.展开更多
文摘The contribution of chronic peripheral inflammation to the pathogenesis of neurodegenerative diseases is an outstanding question. Sustained activation of the peripheral innate and adaptive immune systems occurs in the context of a broad array of disorders ranging from chronic infectious diseases to autoimmune and metabolic diseases. In addition, progressive systemic inflammation is increasingly recognized during aging. Peripheral immune cells could potentially modulate the cellular brain environment via the secretion of soluble molecules. There is an ongoing debate whether peripheral immune cells have the potential to migrate into the brain under certain permissive circumstances. In this perspective, we discuss the possible contribution of chronic peripheral inflammation to the pathogenesis of age-related neurodegenerative diseases with a focus on microglia, the resident immune cells of the brain parenchyma.
基金support from the Boettcher Foundation and the National Institutes of Health(1K99HD111686).
文摘Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic mutations.Traditionally,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth syndromes.More recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental exposures.Here,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and homeostasis.Although the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our knowledge.We will provide current definitions and an overview of contemporary detection approaches for genomic mosaicism.Finally,we will discuss the impact and utility of genomic mosaicism.
