神经退行性疾病分子病理学研究进展
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Nat Rev Neurosci 2003, 4:49-60
神经退行性疾病：蛋白质异常聚集
Nat Rev Neurosci 2003, 4:49-60
Abnormal Accumulation of Proteins in the Brain Is Dependent on Their Production and Clearance
Intracytoplasmic aggregates are typically present in the neurons of people affected by Parkinson’s disease and amyotrophic lateral sclerosis.
Intranuclear inclusions of huntingtin are observed in Huntington’s disease patients
• Huntington’s disease:
Huntingtin protein
➢ inherited autosomal dominant disorder ➢ motor impairment, personality changes ➢ polyglutamine repeat in the Huntingtin protein of some people
Down syndrome
Selkoe et al, 2001
蛋白质折叠异常影响蛋白质的降解和清除
Soluble misfolded monomers and dimers can be recognized by both the UPS or CMA(chaperone-mediated autophagy)-related chaperones, and subsequently degraded by either of these two pathways. In the case of CMA, cytosolic proteins (i.e., asynuclein) are recognized by a chaperone (i.e., Hsc70), which delivers the target protein to the lysosome via a receptor protein present in the lysosomal membrane. However, on more complex assembly (oligomer or fibril formation) of the target protein, macroautophagy is the only mechanism available to clear the more insoluble and highly ordered aggregates.
神经退行性疾病分子病理学 研究进展
课程提纲
• 神经退行性疾病的病理变化 • 神经退行性疾病的致病因素及其机制 • 神经退行性疾病的研究进展
课程提纲
• 神经退行性疾病的病理变化 • 神经退行性疾病的致病因素及其机制 • 神经退行性疾病的研究进展
神经退行性疾病
神经退行性疾病（neurodegenerative diseases） 是一类慢性、随着年龄增长而进行性加重的神经 系统疾病，由神经退行性病变而引起。
Selkoe et al, 2001
基因突变或过表达可导致相关蛋白生成增加
Amyloid Precursor Protein (APP) and Its Processing
Selkoe et al, 2001
基因突变或过表达可导致相关蛋白生成增加
Amyloid Precursor Protein (APP) and Its Processing
Protein deposition in the brain of different types of neurodegenerative diseases
Cerebral aggregates in neurodegenerative diseases
Extracellular amyloid plaques (white arrows) and intracytoplasmic neurofibrillary tangles (yellow arrows) are the pathological signature of Alzheimer’s disease.
AβDP: Aβ-degrading protease UPS Autophห้องสมุดไป่ตู้gy
Cold Spring Harb Perspect Med 2012, 2(6):a006379
基因突变或过表达可导致相关蛋白生成增加
Amyloid Precursor Protein (APP) and Its Processing
Extracellular prion amyloid plaques that are located in different brain regions are present in some cases of transmissible spongiform encephalopathy.
In spite of the different protein compositions, the ultrastructure of these deposits seems to be similar and composed mainly of a network of fibrillar polymers (centre).
Neurodegeneration is the term for the progressive loss of
structure or function of neurons, including death of neurons.
常见神经退行性疾病
Nat Rev Neurosci 2003, 4:49-60
神经退行性疾病：蛋白质异常聚集
Nat Rev Neurosci 2003, 4:49-60
Abnormal Accumulation of Proteins in the Brain Is Dependent on Their Production and Clearance
Intracytoplasmic aggregates are typically present in the neurons of people affected by Parkinson’s disease and amyotrophic lateral sclerosis.
Intranuclear inclusions of huntingtin are observed in Huntington’s disease patients
• Huntington’s disease:
Huntingtin protein
➢ inherited autosomal dominant disorder ➢ motor impairment, personality changes ➢ polyglutamine repeat in the Huntingtin protein of some people
Down syndrome
Selkoe et al, 2001
蛋白质折叠异常影响蛋白质的降解和清除
Soluble misfolded monomers and dimers can be recognized by both the UPS or CMA(chaperone-mediated autophagy)-related chaperones, and subsequently degraded by either of these two pathways. In the case of CMA, cytosolic proteins (i.e., asynuclein) are recognized by a chaperone (i.e., Hsc70), which delivers the target protein to the lysosome via a receptor protein present in the lysosomal membrane. However, on more complex assembly (oligomer or fibril formation) of the target protein, macroautophagy is the only mechanism available to clear the more insoluble and highly ordered aggregates.
神经退行性疾病分子病理学 研究进展
课程提纲
• 神经退行性疾病的病理变化 • 神经退行性疾病的致病因素及其机制 • 神经退行性疾病的研究进展
课程提纲
• 神经退行性疾病的病理变化 • 神经退行性疾病的致病因素及其机制 • 神经退行性疾病的研究进展
神经退行性疾病
神经退行性疾病（neurodegenerative diseases） 是一类慢性、随着年龄增长而进行性加重的神经 系统疾病，由神经退行性病变而引起。
Selkoe et al, 2001
基因突变或过表达可导致相关蛋白生成增加
Amyloid Precursor Protein (APP) and Its Processing
Selkoe et al, 2001
基因突变或过表达可导致相关蛋白生成增加
Amyloid Precursor Protein (APP) and Its Processing
Protein deposition in the brain of different types of neurodegenerative diseases
Cerebral aggregates in neurodegenerative diseases
Extracellular amyloid plaques (white arrows) and intracytoplasmic neurofibrillary tangles (yellow arrows) are the pathological signature of Alzheimer’s disease.
AβDP: Aβ-degrading protease UPS Autophห้องสมุดไป่ตู้gy
Cold Spring Harb Perspect Med 2012, 2(6):a006379
基因突变或过表达可导致相关蛋白生成增加
Amyloid Precursor Protein (APP) and Its Processing
Extracellular prion amyloid plaques that are located in different brain regions are present in some cases of transmissible spongiform encephalopathy.
In spite of the different protein compositions, the ultrastructure of these deposits seems to be similar and composed mainly of a network of fibrillar polymers (centre).
Neurodegeneration is the term for the progressive loss of
structure or function of neurons, including death of neurons.
常见神经退行性疾病
Nat Rev Neurosci 2003, 4:49-60