Dear Editor,A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring homeostasis.This response is largely mediated by the concerted action of p...Dear Editor,A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring homeostasis.This response is largely mediated by the concerted action of pattern recognition receptors(PRRs).Such cooperativity has been described for Toll-like receptors(TLRs)and NACHT,LRR,and pyrin domain-containing protein 3(NLRP3),but the underlying molecular mechanisms remain incompletely understood.Inflammasomes are multi-protein complexes defined by a cytosolic innate immune sensor,usually a PRR,which recruits the adaptor molecule apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)to activate the effector caspase-1 leading to the release of matured IL-1βand IL-18.Active caspase-1 further cleaves gasdermin D(GSDMD)allowing the N-terminal domain of GSDMD(GSDMD-N)to form pores in the plasma membrane,thus facilitating the release of matured IL-1βand IL-18.Pore-forming GSDMD-N further induces pyroptosis,an inflammatory form of cell death.展开更多
Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Park...Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.展开更多
基金Deutsche Forschungsgemeinschaft(DFG CRC 1123[B3],DI-722/16-1[ID:428668490]Munich Cluster for Systems Neurology[SyNergy,EXC 2145])Vascular Dementia Research Foundation to M.Dichgans.Y.Asare was supported by DFG(CRC 1123[B3])+1 种基金J.Bernhagen received funding from DFG/CRC 1123[A3],DFG INST 409/209-1 FUGG,and DFG(EXC 2145 SyNergy)C.Weber was supported by DFG(CRC 1123[A01&A10]).
文摘Dear Editor,A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring homeostasis.This response is largely mediated by the concerted action of pattern recognition receptors(PRRs).Such cooperativity has been described for Toll-like receptors(TLRs)and NACHT,LRR,and pyrin domain-containing protein 3(NLRP3),but the underlying molecular mechanisms remain incompletely understood.Inflammasomes are multi-protein complexes defined by a cytosolic innate immune sensor,usually a PRR,which recruits the adaptor molecule apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)to activate the effector caspase-1 leading to the release of matured IL-1βand IL-18.Active caspase-1 further cleaves gasdermin D(GSDMD)allowing the N-terminal domain of GSDMD(GSDMD-N)to form pores in the plasma membrane,thus facilitating the release of matured IL-1βand IL-18.Pore-forming GSDMD-N further induces pyroptosis,an inflammatory form of cell death.
文摘Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.
