Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include...Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.展开更多
Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson...Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.展开更多
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood ...Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood disorders. A hallmark of PD is the accumulation of alpha-synuclein, a presynaptic neuronal protein that aggregates to form Lewy bodies, leading to neuronal dysfunction and cell death. The study of alpha-synuclein and its pathological forms is crucial for understanding the etiology of PD and developing effective diagnostic and therapeutic strategies. Analytical techniques play a pivotal role in elucidating the structure, function, and aggregation mechanisms of alpha-synuclein. Biochemical methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA) are employed to detect and quantify alpha-synuclein in biological samples, offering insights into its expression levels and post-translational modifications. Imaging techniques like immunohistochemistry and positron emission tomography (PET) allow for the visualization of alpha-synuclein aggregates in tissue samples and in vivo, respectively, facilitating the study of its spatial distribution and progression in PD Spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, provide detailed structural information on alpha-synuclein and its isoforms, aiding in the identification of conformational changes associated with aggregation. Emerging techniques such as cryo-electron microscopy (Cryo-EM) and single-molecule fluorescence enable high-resolution structural analysis and real-time monitoring of alpha-synuclein aggregation dynamics, respectively. The application of these analytical techniques has significantly advanced our understanding of the pathophysiological role of alpha-synuclein in PD. They have contributed to the identification of potential biomarkers for early diagnosis and the evaluation of therapeutic interventions targeting alpha-synuclein aggregation. Despite technical limitations and challenges in clinical translation, ongoing advancements in analytical methodologies hold promise for improving the diagnosis, monitoring, and treatment of Parkinson’s disease through a deeper understanding of alpha-synuclein pathology.展开更多
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN)。
文摘Parkinson's disease(PD)is the second most common neurodegenerative disorder.The clinical manifestations of PD include motor symptoms,such as bradykinesia,resting tremor,rigidity,and nonmotor symptoms,which include disturbances in sleep,gastrointestinal function,and olfaction.PD misdiagnosis rates have been reported to reach approximately 30%,partly owing to the heterogeneity of parkinsonism with non-PD pathologies,and the differential diagnosis of PD from neurodegenerative diseases such as multiple systemic atrophy(MSA)and progressive supranuclear palsy poses another unmet need.
基金supported by the Spanish Ministry of Science and Innovation via a doctoral grant[FPU22/03656].supported by the Spanish Ministry of Science and Innovation(PID2022-137963OB-I00)Generalitat de Catalunya(2021-SGR-00635 AGAUR)+1 种基金CERCA Programme(Generalitat de Catalunya)by ICREA,ICREA-Academia 2020(to SV)。
文摘Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.
文摘Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia, as well as non-motor symptoms including cognitive impairment and mood disorders. A hallmark of PD is the accumulation of alpha-synuclein, a presynaptic neuronal protein that aggregates to form Lewy bodies, leading to neuronal dysfunction and cell death. The study of alpha-synuclein and its pathological forms is crucial for understanding the etiology of PD and developing effective diagnostic and therapeutic strategies. Analytical techniques play a pivotal role in elucidating the structure, function, and aggregation mechanisms of alpha-synuclein. Biochemical methods such as Western blotting and enzyme-linked immunosorbent assay (ELISA) are employed to detect and quantify alpha-synuclein in biological samples, offering insights into its expression levels and post-translational modifications. Imaging techniques like immunohistochemistry and positron emission tomography (PET) allow for the visualization of alpha-synuclein aggregates in tissue samples and in vivo, respectively, facilitating the study of its spatial distribution and progression in PD Spectroscopic methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, provide detailed structural information on alpha-synuclein and its isoforms, aiding in the identification of conformational changes associated with aggregation. Emerging techniques such as cryo-electron microscopy (Cryo-EM) and single-molecule fluorescence enable high-resolution structural analysis and real-time monitoring of alpha-synuclein aggregation dynamics, respectively. The application of these analytical techniques has significantly advanced our understanding of the pathophysiological role of alpha-synuclein in PD. They have contributed to the identification of potential biomarkers for early diagnosis and the evaluation of therapeutic interventions targeting alpha-synuclein aggregation. Despite technical limitations and challenges in clinical translation, ongoing advancements in analytical methodologies hold promise for improving the diagnosis, monitoring, and treatment of Parkinson’s disease through a deeper understanding of alpha-synuclein pathology.
