Banerjee Aniruddha, Thekkekkara Dithu, Manjula S N, Nair Salini P, Lalitha Mankala Sree
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysore, Karnataka 570 015 India.
3 Biotech. 2025 May;15(5):139. doi: 10.1007/s13205-025-04306-5. Epub 2025 Apr 23.
Autophagy disruption is important in Alzheimer's disease (AD) as it prevents misfolded proteins from being removed, which leads to the accumulation of amyloid plaques and neurofibrillary tangles (NFTs). Restoring autophagy improves neuronal survival and cognitive function, according to experimental models. In AD models, mTOR inhibition and AMPK activation enhance synaptic plasticity and lessen learning deficits. Inhibitors of phosphodiesterase-4 (PDE4) improve cognition and reduce neuroinflammation via altering cyclic adenosine monophosphate (cAMP) transmission. Furthermore, autophagic-lysosomal clearance is encouraged by upregulating transcription factor EB (TFEB), which lessens the pathogenic damage linked to AD. These results point to autophagy modification as a promising therapeutic approach, with the mTOR, AMPK, cAMP, and TFEB pathways being possible targets for drugs. Though much evidence is based on animal studies, these findings provide valuable insights into autophagy's role in AD pathology, offering promising directions for future research and drug development.
自噬功能紊乱在阿尔茨海默病（AD）中至关重要，因为它会阻止错误折叠的蛋白质被清除，进而导致淀粉样斑块和神经原纤维缠结（NFTs）的积累。根据实验模型，恢复自噬可提高神经元存活率和认知功能。在AD模型中，抑制mTOR和激活AMPK可增强突触可塑性并减轻学习缺陷。磷酸二酯酶-4（PDE4）抑制剂通过改变环磷酸腺苷（cAMP）传递来改善认知并减轻神经炎症。此外，上调转录因子EB（TFEB）可促进自噬-溶酶体清除，从而减轻与AD相关的致病性损伤。这些结果表明自噬调节是一种有前景的治疗方法，mTOR、AMPK、cAMP和TFEB途径可能是药物作用靶点。尽管许多证据基于动物研究，但这些发现为自噬在AD病理中的作用提供了有价值的见解，为未来研究和药物开发提供了有前景的方向。
