Transcription factor EB as a therapeutic target for intracerebral hemorrhage: A review

Intracerebral hemorrhage (ICH) is a devastating neurological disorder. The complex pathophysiology of secondary injuries following ICH has hindered the development of effective targeted therapies. The autophagy-lysosomal pathway (ALP), a crucial cellular mechanism for clearing damaged organelles and toxic protein aggregates, plays a vital role in maintaining neuronal homeostasis. However, dysregulation of the ALP, ranging from insufficient activation to hyperactivity, exacerbates neuronal injury and contributes to poor neurological outcomes after ICH. Transcription factor EB (TFEB), the primary regulator of the ALP, shows significant therapeutic potential for neurological disorders. Following ICH, TFEB mediates essential neuroprotective functions within neurons. Targeting TFEB offers a promising strategy to restore ALP function and ultimately improve ICH outcomes. This review examines TFEB's regulatory roles within neural cells and systematically analyzes the mechanisms leading to ALP impairment after ICH. Additionally, we discuss potential TFEB-targeted therapeutic interventions, providing valuable insights for the clinical translation of TFEB modulators in ICH treatment.