Gene expression with corresponding pathways analysis in Gaucher disease

Pawliński, Łukasz; Polus, Anna; Kałużna, Małgorzata; Sordyl, Maria; Tobór-Świętek, Ewa; Krawczyk, Magdalena; Bednarek, Marcin; Solnica, Bogdan; Ruchała, Marek; Kieć‐Wilk, Beata

doi:10.1016/j.yexmp.2021.104679

Cited by 4 publications

(4 citation statements)

References 19 publications

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“…In accordance with these findings, we detected and verified the interaction of FLOT1/FLOT2 with guanine-nucleotidebinding protein subunit beta-4 (GNB4), a beta subunit of heterotrimeric G-proteins 77 . Variants of GNB4 were shown to cause Charcot-Marie-Tooth disease 78 , and downregulation of GNB4 levels has been found in Gaucher Disease, a lysosomal storage disorder 79 . Association of GNB4 with lysosomes was implicated in a previous study 80 , and a yeast two-hybrid screen revealed its direct interaction with LAMP2 81 , which co-localizes with FLOT1 and the lysosomal surface 51 .…”

Section: Discussionmentioning

confidence: 99%

Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo

et al. 2022

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Lysosomes are well-established as the main cellular organelles for the degradation of macromolecules and emerging as regulatory centers of metabolism. They are of crucial importance for cellular homeostasis, which is exemplified by a plethora of disorders related to alterations in lysosomal function. In this context, protein complexes play a decisive role, regulating not only metabolic lysosomal processes but also lysosome biogenesis, transport, and interaction with other organelles. Using cross-linking mass spectrometry, we analyze lysosomes and early endosomes. Based on the identification of 5376 cross-links, we investigate protein-protein interactions and structures of lysosome- and endosome-related proteins. In particular, we present evidence for a tetrameric assembly of the lysosomal hydrolase PPT1 and a heterodimeric structure of FLOT1/FLOT2 at lysosomes and early endosomes. For FLOT1-/FLOT2-positive early endosomes, we identify >300 putative cargo proteins and confirm eleven substrates for flotillin-dependent endocytosis, including the latrophilin family of adhesion G protein-coupled receptors.

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Section: Discussionmentioning

confidence: 99%

Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo

et al. 2022

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“…NTRK1 has been reported to contribute to neuronal survival, differentiation, and development [ 23 , 24 ], which encouraged the present investigation of whetherNTRK1was involved in the regulation of the CI due to HND. Therefore, a series of systematic experiments were conducted in this study, which revealed thatNTRK1 knockdown induced mouse CI and mouse HND.…”

Section: Discussionmentioning

confidence: 97%

“…3 ) indicated that NTRK1 knockdown weakened the viability and enhanced the apoptosis of the isolated mouse hippocampal neurons. Previous studies indicated the neuroprotective functions of NTRK1 [ 10 , 11 , 23 , 24 ]. So consistently, our findings also indicated the neuroprotective role of NTRK1 on hippocampal neurons.…”

Section: Discussionmentioning

confidence: 99%

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway

Yang,

Wu,

et al. 2023

Cell Death Discov.

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Hippocampal neuronal damage may induce cognitive impairment. Neurotrophic tyrosine kinase receptor 1 (NTRK1) reportedly regulates neuronal damage, although the underlying mechanism remains unclear. The present study aimed to investigate the role of NTRK1 in mouse hippocampal neuronal damage and the specific mechanism. A mouse NTRK1-knockdown model was established and subjected to pre-treatment with BAY-3827, followed by a behavioral test, Nissl staining, and NeuN immunofluorescence (IF) staining to evaluate the cognitive impairment and hippocampal neuronal damage. Next, an in vitro analysis was conducted using the CCK-8 assay, TUNEL assay, NeuN IF staining, DCFH-DA staining, JC-1 staining, ATP content test, mRFP-eGFP-LC3 assay, and LC3-II IF staining to elucidate the effect of NTRK1 on mouse hippocampal neuronal activity, apoptosis, damage, mitochondrial function, and autophagy. Subsequently, rescue experiments were performed by subjecting the NTRK1-knockdown neurons to pre-treatment with O304 and Rapamycin. The AMPK/ULK1/FUNDC1 pathway activity and mitophagy were detected using western blotting (WB) analysis. Resultantly, in vivo analysis revealed that NTRK1 knockdown induced mouse cognitive impairment and hippocampal tissue damage, in addition to inactivating the AMPK/ULK1/FUNDC1 pathway activity and mitophagy in the hippocampal tissues of mice. The treatment with BAY-3827 exacerbated the mouse depressive-like behavior induced by NTRK1 knockdown. The results of in vitro analysis indicated that NTRK1 knockdown attenuated viability, NeuN expression, ATP production, mitochondrial membrane potential, and mitophagy, while enhancing apoptosis and ROS production in mouse hippocampal neurons. Conversely, pre-treatment with O304 and rapamycin abrogated the suppression of mitophagy and the promotion of neuronal damage induced upon NTRK1 silencing. Conclusively, NTRK1 knockdown induces mouse hippocampal neuronal damage through the suppression of mitophagy via inactivating the AMPK/ULK1/FUNDC1 pathway. This finding would provide insight leading to the development of novel strategies for the treatment of cognitive impairment induced due to hippocampal neuronal damage.

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“…Various mechanisms have been proposed for the beneficial effects of KD, including the modulation of inflammatory signaling pathways such as NF-κB [ 202 ], NLRP3 inflammasome [ 203 , 204 ], and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway [ 205 ], all of which have been reported to be disturbed in FD [ 206 , 207 ], and other LDSs [ 208 , 209 ]. Additionally, KD has been associated with improved mitochondrial function and ATP production [ 210 , 211 ].…”

Section: Nutritional Strategies In Fabry Disease Managementmentioning

confidence: 99%

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Weissman,

Dudek,

Sequeira

et al. 2024

Curr Heart Fail Rep

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Purpose of Review This review explores the interplay among metabolic dysfunction, oxidative stress, inflammation, and fibrosis in Fabry disease, focusing on their potential implications for cardiac involvement. We aim to discuss the biochemical processes that operate in parallel to sphingolipid accumulation and contribute to disease pathogenesis, emphasizing the importance of a comprehensive understanding of these processes. Recent Findings Beyond sphingolipid accumulation, emerging studies have revealed that mitochondrial dysfunction, oxidative stress, and chronic inflammation could be significant contributors to Fabry disease and cardiac involvement. These factors promote cardiac remodeling and fibrosis and may predispose Fabry patients to conduction disturbances, ventricular arrhythmias, and heart failure. While current treatments, such as enzyme replacement therapy and pharmacological chaperones, address disease progression and symptoms, their effectiveness is limited. Summary Our review uncovers the potential relationships among metabolic disturbances, oxidative stress, inflammation, and fibrosis in Fabry disease–related cardiac complications. Current findings suggest that beyond sphingolipid accumulation, other mechanisms may significantly contribute to disease pathogenesis. This prompts the exploration of innovative therapeutic strategies and underscores the importance of a holistic approach to understanding and managing Fabry disease.

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Gene expression with corresponding pathways analysis in Gaucher disease

Cited by 4 publications

References 19 publications

Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo

Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo

NTRK1 knockdown induces mouse cognitive impairment and hippocampal neuronal damage through mitophagy suppression via inactivating the AMPK/ULK1/FUNDC1 pathway

Fabry Disease: Cardiac Implications and Molecular Mechanisms

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