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The progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the accumulation of α-synuclein aggregates within Lewy bodies (LBs) are the neuropathological hallmarks of Parkinson’s disease (PD). Abnormal α-synuclein accumulation and cellular dysfunction of cytosolic organelles like mitochondria, lysosomes, and the endoplasmatic reticulum (ER) occur in a vicious circle that promotes progressive spatiotemporal neurodegeneration. Moreover, a combination of genetic, epigenetic, and environmental factors increases the risk of developing PD. The interplay of α-synuclein aggregates with cellular functions and the mechanism that underlies the pathological α-synuclein spreading in the nervous system are discussed in this chapter. A more detailed discussion of the individual key pathophysiological mechanisms is given in the following chapters.

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Pathophysiological Basis of Neurodegeneration in Parkinson’s Disease

  • 实验方案

  • 发表日期：

    2025年

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  • Lara Sophia Molina Galindo,
  • Gabriel Gonzalez-Escamilla,
  • Sergiu Groppa

摘要

The progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the accumulation of α-synuclein aggregates within Lewy bodies (LBs) are the neuropathological hallmarks of Parkinson’s disease (PD). Abnormal α-synuclein accumulation and cellular dysfunction of cytosolic organelles like mitochondria, lysosomes, and the endoplasmatic reticulum (ER) occur in a vicious circle that promotes progressive spatiotemporal neurodegeneration. Moreover, a combination of genetic, epigenetic, and environmental factors increases the risk of developing PD. The interplay of α-synuclein aggregates with cellular functions and the mechanism that underlies the pathological α-synuclein spreading in the nervous system are discussed in this chapter. A more detailed discussion of the individual key pathophysiological mechanisms is given in the following chapters.