文档介绍：Drugs Used for Neurodegenerative Diseases S 治疗中枢神经系统 退行性疾病药物
Neurodegenerative Diseases
Associated with progressive loss of neurons and their functions
Parkinson’s disease(帕金森病)
Alzheimer’s disease(阿尔茨海默病)
Huntington’s disease(亨廷顿病,舞蹈病)
Amyotrophic lateral sclerosis (肌萎缩侧索硬化症)
Common Mechanisms of Neurodegeneration
Misfolded and aggregated proteins
-synuclein in PD;
-amyloid and tau in AD;
huntingtin in HD;
SOD and TDP-43 in ALS
Excess glutamate in the brain
Impairment in the capacity of neurons for oxidative metabolism
Parkinsonism (Parkinson’s syndrome)
not resulted from neurodegenerative disease
used to describe the syndrome
Parkinson's disease
the second most prevalent neurodegenerative disease (after Alzheimer's disease)
the mon cause of parkinsonism
Parkinson’s disease
Symptoms:
Resting tremor
Muscle rigidity ---- increased tone, akinesia运动不能
Bradykinesia运动徐缓-----difficulty in initiating movements and controlling fine movements
Postural instability
Parkinson’s disease
Background:
1. Neuronal circuits involved in movements:
cortical regions, thalamus丘脑, cerebellum小脑, and basal ganglia基底节(substantia nigra黑质, striatum纹状体, globus pallidus苍白球 and subthalamus下丘脑).
striatum: caudate nucleus 尾核and putamen壳核
2. The basal ganglia play an important part in the initiation and scaling of movement.
Dopamine pathways
Parkinson’s disease
Background:
3. Dopamine neurons in the substantia nigra project to the striatum纹状体(caudate nucleus and putamen) and exert an inhibitory influence on motoneurons.
4. Cholinergic interneurons in the striatum纹状体promote motoneuronal excitation