bims-lycede Biomed News
on Lysosome-dependent cell death
Issue of 2025–06–01
two papers selected by
Sofía Peralta, Universidad Nacional de Cuyo



  1. Antioxidants (Basel). 2025 May 20. pii: 611. [Epub ahead of print]14(5):
      Lysosomal storage diseases (LSDs) are characterized by the accumulation of undegraded substrates within lysosomes, often associated with oxidative stress and impaired lysosomal function. In this study, we investigate the role of the c-Abl/TFEB pathway in different LSDs: Gaucher, Niemann-Pick type A (NPA), and Niemann-Pick type C (NPC). Our findings identify c-Abl activation (p-c-Abl) as a common pathogenic mechanism in these disorders. We demonstrate that c-Abl phosphorylates TFEB at Tyr173, leading to its cytoplasmic retention. Using pharmacological models of Gaucher, NPA and NPC in SH-SY5Y neuronal cells and HeLa cells, we assess the effects of the c-Abl inhibitors Imatinib and Neurotinib, as well as the antioxidant α-Tocopherol (α-TOH), on TFEB nuclear translocation and p-c-Abl protein levels. Additionally, we explore the effects of c-Abl inhibitors in cholesterol accumulation in LSDs neuronal models. Our results show that treatment with c-Abl inhibitors or α-TOH promotes TFEB nuclear translocation, enhances lysosomal clearance, and reduces cholesterol accumulation in all three LSD models. These findings highlight the c-Abl/TFEB pathway as a potential therapeutic target for LSDs and potentially other neurodegenerative disorders associated with lysosomal dysfunction.
    Keywords:  Gaucher; Imatinib; Neurotinib; Niemann-Pick; c-Abl; lysosomal storage diseases; transcription factor EB; α-Tocopherol
    DOI:  https://doi.org/10.3390/antiox14050611
  2. Int J Gen Med. 2025 ;18 2539-2552
       Background: Transcription factor EB (TFEB) is an endogenous protective protein. Serum TFEB levels were measured after acute intracerebral hemorrhage (ICH), in addition to determining their connection to the severity and neurological outcomes of patients.
    Methods: Serum TFEB levels were measured in a prospective cohort study of 186 ICH patients and 100 controls. Severity was estimated using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. Poor neurological status mirrored by the post-ICH six-month modified Rankin Scale (mRS), along with stroke-associated pneumonia (SAP), was considered as the two outcome variables.
    Results: Patients showed a marked decline in serum TFEB levels compared with controls. Serum TFEB levels were significantly inversely correlated with both NIHSS scores and hematoma volume; had a linear relationship with likelihoods of both SAP and poor prognosis (mRS scores 3-6), were independent of ordinal mRS scores, SAP, and poor prognosis; and were efficiently predictive of SAP and poor prognosis with analogous areas under the receiver operating characteristic curve as NIHSS scores and hematoma volume. The association between serum TFEB levels and poor prognosis is partly mediated by SAP.
    Conclusion: Reduced serum TFEB levels post-ICH of evident relevance to bleeding intensity are powerfully linked to poor neurological prognosis, wherein there is a partial mediative effect by SAP, thereby reinforcing TFEB as a serological prognostic indicator of good prospect in ICH.
    Keywords:  biomarkers; intracerebral hemorrhage; outcome; severity; stroke-associated pneumonia; transcription factor EB
    DOI:  https://doi.org/10.2147/IJGM.S519757