中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (6): 2306-2317.doi: 10.4103/NRR.NRR-D-24-01571

• 综述:退行性病与再生 • 上一篇    下一篇

突触线粒体在衰老和神经退行性疾病中的作用:揭示其功能衰退和脆弱性

  

  • 出版日期:2026-06-15 发布日期:2025-09-18

Synaptic mitochondria in aging and neurodegenerative diseases: Functional decline and vulnerability

Karina A. Cicali1, 2, Angie K. Torres1, 3, Cheril Tapia-Rojas1, 2, *   

  1. 1 Laboratory of Neurobiology of Aging, Centro Científico y Tecnológico de Excelencia Ciencia & Vida, Fundación Ciencia & Vida, Santiago, Chile;  2 Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile;  3 Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile
  • Online:2026-06-15 Published:2025-09-18
  • Contact: Cheril Tapia-Rojas, PhD, cheril.tapia@uss.cl.
  • Supported by:
    This work was supported by ANID FONDECYT No. 1221178 and Centro Ciencia & Vida, FB210008, Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.

摘要: https://orcid.org/0000-0002-7084-0318 (Cheril Tapia-Rojas)

Abstract: Aging is a physiological and complex process produced by accumulative age-dependent cellular damage, which significantly impacts brain regions like the hippocampus, an essential region involved in memory and learning. A crucial factor contributing to this decline is the dysfunction of mitochondria, particularly those located at synapses. Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites. In contrast, non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply. Both pools of mitochondria differ in their form, proteome, functionality, and cellular role. The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics, transport, and quality control. However, synaptic mitochondria are particularly vulnerable to age-associated damage, characterized by oxidative stress, impaired energy production, and calcium dysregulation. These changes compromise synaptic transmission, reducing synaptic activity and cognitive decline during aging. In the context of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, the decline of synaptic mitochondrial function is even more pronounced. These diseases are marked by pathological protein accumulation, disrupted mitochondrial dynamics, and heightened oxidative stress, accelerating synaptic dysfunction and neuronal loss. Due to their specialized role and location, synaptic mitochondria are among the first organelles to exhibit dysfunction, underscoring their critical role in disease progression. This review delves into the main differences at structural and functional levels between synaptic and nonsynaptic mitochondria, emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration. These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration. This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria, highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.

Key words: aging, hippocampus, memory, mitochondria, synaptic mitochondria