The growing global population and increasing longevity have led to a surge in neurodegenerative diseases (NDs), contributing to higher rates of morbidity and mortality. Neurodegenerative diseases like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD) share a common pathology of neuronal damage caused by the accumulation of toxic proteins. Meeting the escalating clinical demands, the real-time monitoring of neuronal mitochondria has emerged as an imperative requirement for the advancement of ND drug development. Mitochondrial dysfunction significantly influences the initiation and progression of NDs. Primary mitochondrial abnormalities manifest before the aggregation of toxic proteins and the onset of clinical symptoms. As these diseases advance, toxic proteins progressively accumulate, leading to secondary mitochondrial dysfunction, including compromised enzyme activity and altered mitochondrial protein equilibrium. Advanced stages of ND witness aggravated mitochondrial impairment, where severe dysfunction can culminate in neuronal demise and cognitive decline. In this context, visualizing the mitochondrial status of neurons holds pivotal significance in monitoring ND progression and assessing the effectiveness of potential drug candidates. Fluorescence microscopy imaging offers a suite of benefits such as high sensitivity, user-friendliness, and precise temporal and spatial resolution. Consequently, it has gained extensive application in exploring mitochondrial function. The integration of fluorescent imaging platforms, comprising probes and microscopes, introduces novel avenues for accurate ND diagnosis and the evaluation of drug candidates by dynamically tracking shifts in mitochondrial morphology and function.
The research team, led by Professor Li Cong from the School of Pharmacy, has meticulously compiled a comprehensive overview of recent advancements in fluorescent imaging tools designed to target ND-related mitochondrial dysfunction. Their study titled "Fluorescence Microscopy Platforms for Visualizing Mitochondrial Abnormalities in Neurodegenerative Diseases" has been published in the journal Advanced Drug Delivery Reviews. This groundbreaking research sheds light on the atypical traits displayed by neuron mitochondria across metabolism, structure, and function during the evolution of neurodegenerative diseases. The review delineates a multi-dimensional fluorescence microscopy platform, spanning various scales, for real-time tracking of mitochondrial anomalies. Furthermore, it presents an exhaustive compilation of techniques to visualize aberrations in mitochondrial structure, metabolism, and function. The review culminates by addressing the challenges posed by fluorescence microscopy in effectively monitoring ND progression and designing mitochondria-targeted therapeutics.
This review represents a significant stride towards enhancing our understanding of the intricate relationship between mitochondrial abnormalities and neurodegenerative diseases. By spotlighting the potential of fluorescence microscopy platforms, this work not only propels ND research forward but also paves the way for innovative therapeutic strategies.
Yicheng Wang and Pengwei Wangof the School of Pharmacy, Fudan University are the co-first authors of the paper. Professor Cong Li from the School of Pharmacy, Fudan University is the corresponding author. This work was supported by the National Natural Science Foundation of China, the National Science Fund for Distinguished Young Scholars and the Program of Shanghai Science and Technology Committee. Original link: https://doi.org/10.1016/j.addr.2023.114841.
