LRRK2 (Leucine Rich Repeat Kinase 2)

Therapeutic agents that modulate pathways such as ephrin, cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), Hippo, Receptor-Interacting Protein Kinase 1 (RIPK1), Leucine-rich repeat kinase 2 (LRRK2), and sirtuin pathways have shown anti-inflammatory effects in PD models. Combining approaches targeting immune and cytokine pathways offers a promising strategy for neuroprotection and disease modification in PD.

Regarding genetic PD patients, the most common cancer types in the LRRK2 and GBA1 groups were skin cancer and lymphoma, while PRKN/PARK2 carriers appeared with an overall increased incidence of cancer. No statistically significant results were observed comparing cancer incidence in PD patients to that in healthy control individuals. Interesting results were obtained by dividing the patients by gender, showing increased cancer risk in female PD patients and female LRRK2 carriers, along with increased breast cancer risk in female PD patients compared to healthy controls.

Drug enrichment analysis predicted potential therapeutic compounds, especially sunitinib targeting LRRK2...The diagnostic model based on the six ExoNSCLC-DEGs has strong diagnostic performance and clinical applicability. In-depth research on ExoNSCLC-DEGs provides new insights into the pathogenesis of NSCLC and provides new directions for subsequent research.

Additionally, multiple Parkinson's disease-related genes, including VPS35 and LRRK2, also regulate MAPL-induced pyroptosis. Notably, depletion of MAPL, LRRK2 or VPS35 inhibited inflammatory cell death in primary macrophages, placing MAPL and the mitochondria-lysosome pathway at the nexus of immune signalling and cell death.

FBXO45 is a key E3 ubiquitin ligase in ovarian cancer, promoting growth, spread and migration via the Wnt/β-catenin pathway. Ubiquitination-related markers provide reliable prognostic insights and reflect the immune microenvironment in ovarian cancer, offering a basis for clinical targeting strategies.

YWHAG drives NSCLC progression by promoting EMT, proliferation, and metastasis via the LRRK2/PI3K/AKT axis. Its pan-cancer overexpression and prognostic significance highlights YWHAG as a promising therapeutic target in lung cancer.

MTHFD2 targeted LRRK2 to alter NSCLC cell phenotypes in vitro and growth in vivo. Our findings demonstrate for the first time the protumorigenic role of the YY1/MTHFD2/LRRK2 cascade in NSCLC.

Furthermore, LRRK2 overexpression significantly increased both the colony formation and cell invasion rates in AML cells, compared to the down-regulation of USP7. Taken together, our findings identify USP7 as a novel deubiquitinating enzyme of LRRK2 that positively regulates its stability and plays an oncogenic role in AML, with implications for AML cancer progression and potential therapeutic targets.

Moreover, LRRK2 inhibition also enhances the activity of other lysosomal hydrolases. Our findings expand the understanding of the molecular mechanism of LRRK2 inhibitors, offering valuable insights for further development of PD treatments.

Crucially, these protective effects and pathway activation were abolished in GPNMB KO mice.ConclusionsLncRNA LINKA may protect against HALI by activating the GPNMB/HIF-1α signaling pathway, leading to suppressed apoptosis and inflammation. This identifies LncRNA LINKA as a potential therapeutic target for HALI.

This study suggests that PD and cancer may be connected through shared biological pathways, some overlapping with cancer hallmarks, and highlights the need for future mechanistic and functional studies to clarify the role of PD genes in cancer biology.

In summary, our current research revealed a novel SLC34A2/LRRK2/TTF-1/SELENBP1 axis and its involvement in inhibiting the malignant characteristics of LUAD cells for the first time, which made contribution to further exploring the clinical application of SLC34A2. Furthermore, it also might offer novel insights into understanding how AT2 cells undergo malignant transformation into LUAD cells in the future.