To support your ongoing neurodegeneration and oncology research, CST scientists are constantly developing and validating novel antibodies against important targets in relevant applications.
Neurodegenerative diseases, including Alzheimers disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), are characterized by loss of neuronal function and cell death. Understanding the contribution of programmed cell death signaling pathways to disease progression remains a central goal of these fields.
Apoptosis may be initiated via surface death receptors or mitochondrial dysfunction as a result of oxidative stress. Extracellular amyloid plaques and intracellular β-Amyloid can lead to activation of both presynaptic and postsynaptic apoptotic signaling. A number of proapoptotic hallmarks are elevated in neurodegenerative diseases.1
Mutations in the autophagy pathway, including SQSTM1/p62 family members, PTEN-induced putative kinase (PINK1), and Parkin, are associated with neurodegenerative diseases such as PD. Increases in LC3-positive microglia are observed in tissue from patients harboring AD-associated TREM2 mutations and TREM2 KO mice, suggesting that disruption of TREM2-dependent autophagy can contribute to AD etiology.2
Necroptosis is a form of programmed cell death triggered by stress/inflammation and has been found to be activated in AD, multiple sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). Activation and assembly of the necrosome complex containing receptor-interacting protein kinase 1 (RIPK1) and RIPK3 lead to phosphorylation and oligomerization of mixed-lineage kinase domain-like (MLKL), followed by lipid peroxidation, cation influx, and ultimately, cell death.3
The ability to evade programmed cell death is one of the hallmarks of cancer cells. Understanding mechanisms malignant cells use to escape this cellular function increases our comprehension about cancer progression and offers potential therapeutic targets.
Dysregulated apoptosis drives tumorigenesis when there is a loss of balance between cell division and cell death. Reduced apoptosis increases tumor growth and can occur when there is an increase of anti- vs pro-apoptotic Bcl-2 family members, inactivation of tumor suppressors like p53, or upregulation of caspase-inhibiting proteins. Additionally, decreased expression or inactivating mutations in death receptor signaling pathway proteins, like CD95, can decrease apoptosis in malignant cells.4
Phospho-p53 (Ser33) Antibody #2526: Immunohistochemical analysis of paraffin-embedded human breast carcinoma, using Phospho-p53 (Ser33) Antibody.
Bcl-2 (124) Mouse mAb #15071: Immunohistochemical analysis of paraffin-embedded RL-7 (positive, left) and HT-29 (negative, right) cell pellets using Bcl-2 (124) Mouse mAb.
Autophagy is thought to have a dual tumorigenic role. Several autophagy-promoting genes have been found to function as tumor suppressors, including Beclin-1, UVRAG, SQSTM1/p62, and BNIP3. Inhibition of autophagic activity can promote tumor progression through loss of pathogen clearance and damaged organelles. In contrast, autophagy is thought to promote oncogenesis by enabling the survival of nutrient starved cancer cells. Drugs targeting autophagy are currently being evaluated as therapeutic strategies for cancer.5,6
Necroptosis is thought to play multiple roles in cancer. It potentially facilitates metastasis by promoting inflammation of non transformed cells in the tumor microenvironment. Necrotic cells also provide antigens and inflammatory stimulation for the cross-priming required to activate anti-tumor immunity. Necroptosis mediators, like RIPK3, CYLD, and MLKL, are also commonly downregulated in various cancer types including, but not limited to, acute myeloid leukemia, breast carcinoma, and cervical carcinoma.7