Research Progress on the Interaction Between Endoplasmic Reticulum Stress and Autophagy in Neurodegenerative Diseases

The interaction between endoplasmic reticulum (ER) stress and autophagy plays a critical yet complex role in neurodegenerative diseases. This review systematically explores their dynamic regulatory relationships in Alzheimers disease (AD), Parkinsons disease (PD), and related disorders. ER stress modulates autophagy activity through key signaling pathways to maintain neuronal proteostasis, but chronic dysregulation can cause impaired autophagy, accelerating abnormal protein aggregation and neuronal damage. Recent findings reveal that this interaction not only influences early pathological progression but is also closely associated with therapeutic resistance. Although targeted interventions (e.g., pharmacological modulation and novel therapies) have shown promise in preclinical studies, their clinical application remains limited by challenges such as target specificity and delivery efficiency. This review emphasizes the necessity for in-depth analysis of the spatiotemporal dynamics of the ER stress-autophagy network, highlighting that multidisciplinary approaches could unlock new avenues for mechanistic exploration and precision therapy in neurodegenerative diseases, offering significant scientific and translational value.