bims-lycede 2025-08-31 papers

Int J Mol Sci. 2025 Aug 15. pii: 7886. [Epub ahead of print]26(16):

Dominik Lewandowski, Mateusz Konieczny, Agata Różycka, Krzysztof Chrzanowski, Wojciech Owecki, Jan Kalinowski, Mikołaj Stepura, Paweł Jagodziński, Jolanta Dorszewska.

Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington's disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.

Keywords: autophagy; cathepsins; neurodegenerative diseases; neuroinflammation; proteolysis

DOI: https://doi.org/10.3390/ijms26167886

Anal Methods. 2025 Aug 22.

A colorimetric and turn-on fluorescent probe for visualization of lysosomal pH fluctuation.

Xiaofei Yin, Boyang Zhang, Yibin Wang, Ning Du, Zongxing Wang, Jianbu Wang, Qihua You.

Lysosomal pH is important for regulating various physiological processes, and slight fluctuations in lysosomal pH can induce many adverse effects on cellular status, such as inflammation, aging, and tumours. Heat stroke is one of the most serious causes of morbidity and mortality. However, the relationship between heat shock and lysosomal pH values is still poorly understood. Herein, we introduced a colorimetric and turn-on fluorescent probe in the red to NIR range for monitoring lysosomal pH values. The probe can selectively accumulate in lysosomes with a high Pearson's coefficient (0.95), and the suitable pKa value (6.73 ± 0.07) enables the probe to visualize changes in lysosomal pH values during the stimulation by chloroquine and heat stroke, respectively.

DOI: https://doi.org/10.1039/d5ay00791g

Med Rev (2021). 2025 Aug;5(4): 297-317

Spatio-temporal processes in autophagosome-lysosome fusion.

Shizuo Liu, Huan Yan, Jiajie Diao, Shen Zhang, Qing Zhong.

Macroautophagy/autophagy is a lysosome-dependent degradation process involved in cellular energy metabolism, recycling and quality control. Autophagy is a highly dynamic and precisely regulated process, which contains four major steps: autophagic membrane initiation and cargo recognition, autophagosome formation, autophagosome-lysosome fusion and lysosomal degradation. During the terminal phase of autophagy, the merging of the autophagosome and lysosome membranes is critical for the effective breakdown of sequestered cargoes. However, the participated molecules and the interplay among them have not been fully uncovered. The spatiotemporal property of these molecules is crucial for maintaining the orderly fusion of autophagosomes and lysosomes, otherwise it may lead to fusion disorders. In this article, we tend to summarize the molecules mediating autophagosome-lysosome fusion into two categories: effector molecules and regulatory molecules. The effector molecules are soluble N-ethylmaleimide-sensitive factor attachment protein receptor and tethering proteins, and the latter category contains phosphatidylinositol, Rab GTPases and ATG8-family proteins. The spatio-temporal properties of these autophagosome-lysosome fusion mediating molecules will be featured in this review.

Keywords: autophagosome-lysosome fusion; autophagy; sensitive factor attachment protein receptor; syntaxin 17

DOI: https://doi.org/10.1515/mr-2024-0095