Autophagy in neurodegenerative diseases: A double-edged sword in disease progression and therapy

Abstract

Background: Autophagy constitutes a critical catabolic pathway that mediates the degradation and recycling of dysfunctional organelles and cytotoxic protein aggregates. Accumulating evidence indicates its pivotal involvement in the pathogenesis of major neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). This study seeks to systematically investigate global research trends and the underlying intellectual structure pertaining to autophagy in the context of neurodegenerative diseases.

Methods: A total of 5,034 articles published over 20 years were analyzed using CiteSpace (version 6.4.1R), VOSviewer (version 1.6.20), bibliometrix (R package), Scimago Graphica(version 1.0.46.0), and Microsoft Office Excel 2021(version 16.48). Analyses included co-citation, keyword evolution, and collaboration networks.

Results: Over the past two decades, the field has experienced robust growth, with a 24.93% annual publication growth rate and over 224,000 cumulative references. China and the United States led in publication output, with significant international cooperation. Authors such as Rubinsztein DC and Nixon RA were highly cited. Influential journals included Autophagy and Journal of Biological Chemistry. Established research areas include autophagy, neurodegenerative diseases, Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, oxidative stress and apoptosis. keywords analysis emphasizes mitophagy, oxidative stress, and neuroinflammation, with a focus on disease-specific mechanisms and cellular microdomains. The autophagy–mitochondria– lysosome axis has gained prominence, highlighting organelle quality control and its role in neuronal survival, paving the way for integrated, stage-specific therapeutic strategies.

Conclusion: Autophagy is now embedded within disease-specific networks, revealing new insights into disease mechanisms and therapeutic strategies. Its dual role in neuroinflammation, both protective and contributory, adds complexity to its involvement in disease progression. Moving forward, research should refine these insights, targeting disease stages and cellular networks to develop more effective therapies.