Department Of Human Genetics And Molecular Medicine

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Subject: search.filters.subject.Therapeutic strategies

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    Targeting calcium homeostasis and impaired inter-organelle crosstalk as a potential therapeutic approach in Parkinson's disease
    (Elsevier Inc., 2023-08-02T00:00:00) Kaur, Satinder; Sehrawat, Abhishek; Mastana, Sarabjit Singh; Kandimalla, Ramesh; Sharma, Pushpender Kumar; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Current therapeutic strategies for PD are limited and mainly involve symptomatic relief, with no available treatment for the underlying causes of the disease. Therefore, there is a need for new therapeutic approaches that target the underlying pathophysiological mechanisms of PD. Calcium homeostasis is an essential process for maintaining proper cellular function and survival, including neuronal cells. Calcium dysregulation is also observed in various organelles, including the endoplasmic reticulum (ER), mitochondria, and lysosomes, resulting in organelle dysfunction and impaired inter-organelle communication. The ER, as the primary calcium reservoir, is responsible for folding proteins and maintaining calcium homeostasis, and its dysregulation can lead to protein misfolding and neurodegeneration. The crosstalk between ER and mitochondrial calcium signaling is disrupted in PD, leading to neuronal dysfunction and death. In addition, a lethal network of calcium cytotoxicity utilizes mitochondria, ER and lysosome to destroy neurons. This review article focused on the complex role of calcium dysregulation and its role in aggravating functioning of organelles in PD so as to provide new insight into therapeutic strategies for treating this disease. Targeting dysfunctional organelles, such as the ER and mitochondria and lysosomes and whole network of calcium dyshomeostasis can restore proper calcium homeostasis and improve neuronal function. Additionally targeting calcium dyshomeostasis that arises from miscommunication between several organelles can be targeted so that therapeutic effects of calcium are realised in whole cellular territory. � 2023 Elsevier Inc.
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    Translational implications of humoral and cellular immune dysfunction in granulomatosis with polyangiitis
    (Academic Press, 2023-02-20T00:00:00) Singh, Harinder; Kumar, Uma; Senapati, Sabyasachi
    Granulomatosis with polyangiitis (GPA) is a rare systemic ANCA (Anti-neutrophil cytoplasmic antibodies) associated vasculitis (AAV). In the last couple of decades, GPA has emerged as a disease of concern due to rapid increase in the prevalence and incidence especially in developing countries. Unknown aetiology and rapid progression have made GPA a critical disease. Thus, establishing specific tools to facilitate early and faster disease diagnosis and efficient disease management has immense importance. GPA may develop in genetically predisposed individuals on receiving the external stimulus (i.e. microbial pathogen, pollutant etc.) that triggers the immune response. B-cell activating factor (BAFF) produced by the neutrophils, promotes the B-cell maturation and survival which leads to increased ANCA production. Abnormal B-cell and T-cell proliferation and their cytokine response plays a major role in disease pathogenesis and granuloma formation. ANCA interacts with neutrophils and induces the neutrophil extracellular traps (NETs) formation and reactive oxygen species (ROS) production which leads to the endothelial cell injury. This review article summarizes the critical pathological events and how cytokines and immune cells shape the GPA pathogenesis. Decoding this complex network would facilitate in developing tools for diagnosis, prognosis and disease management. Recently developed specific monoclonal antibodies (MAbs) targeting cytokines and immune cells are being used for safer treatment and achieving longer remission. � 2023 Elsevier Ltd