Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology DOI Creative Commons
Hirohisa Watanabe, Sayuri Shima, Kazuya Kawabata

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 22, 2025

Parkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in pentose phosphate pathway purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple functions, require significant due to their dense synaptic activity long-range connections. Deficits ATP production PD can severely impair these hubs. The imbalance also affects subcortical regions, including massive axonal arbors striatum substantia nigra pars compacta neurons, high demand. decline may result α -synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown accelerated neurodegeneration. We propose an “ATP Supply–Demand Mismatch Model” help explain pathogenesis PD. model emphasizes how deficits drive pathological protein aggregation, autophagy, degeneration key networks, contributing both motor non-motor symptoms.

Language: Английский

Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology DOI Creative Commons
Hirohisa Watanabe, Sayuri Shima, Kazuya Kawabata

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 22, 2025

Parkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in pentose phosphate pathway purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple functions, require significant due to their dense synaptic activity long-range connections. Deficits ATP production PD can severely impair these hubs. The imbalance also affects subcortical regions, including massive axonal arbors striatum substantia nigra pars compacta neurons, high demand. decline may result α -synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown accelerated neurodegeneration. We propose an “ATP Supply–Demand Mismatch Model” help explain pathogenesis PD. model emphasizes how deficits drive pathological protein aggregation, autophagy, degeneration key networks, contributing both motor non-motor symptoms.

Language: Английский

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