Immunostimulatory monoclonal antibodies for cancer therapy

Increasing immune responses with immunostimulatory monoclonal antibodies (mAbs) directed to immune-receptor molecules is a new and exciting strategy in cancer therapy. This expanding class of agents functions on crucial receptors, either antagonizing those that suppress immune responses or activating others that amplify immune responses. Complications such as autoimmunity and systemic inflammation are problematic side effects associated with these agents. However, promising synergy has been observed in preclinical models using combinations of immunostimulatory antibodies and other immunotherapy strategies or conventional cancer therapies. Importantly, mAbs of this type have now entered clinical trials with encouraging initial result

Transcriptional mutagenesis by 8-oxodG in α-synuclein aggregation and the pathogenesis of Parkinson’s disease

Parkinson's disease (PD) is an age-related progressive neurodegenerative disease associated with selective loss of dopaminergic neurons. The characteristic hallmark of the disease is intracytoplasmic proteinacious inclusion bodies called Lewy bodies, primarily consisting of a presynaptic protein α-synuclein. Oxidative stress-mediated damage to macromolecules have been shown to occur frequently in PD. Oxidative damage to DNA in the form of oxidized guanine (8-oxodG) accumulates in both the mitochondrial and nuclear DNA of dopaminergic neurons of the substantia nigra in PD. 8-oxodG-mediated transcriptional mutagenesis has been shown to have the potential to alter phenotype of cells through production of mutant pool of proteins. This review comprehensively summarizes the role of oxidative stress-mediated damage incurred during neurodegeneration, and highlights the scope of transcriptional mutagenesis event in leading to α-synuclein aggregation as seen in PD

Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.

Parkinson's disease is a devastating neurological condition that affects at least four million people. A striking feature of this disorder is the preferential loss of dopamine-producing neurons in the midbrain. Several aetiological triggers have been linked to Parkinson's disease, including genetic mutations and environmental toxins, but the pathway that leads to cell death is unknown. Recent developments have shed light on the pathogenic mechanisms that underlie the degeneration of these cells. We propose that defective sequestration of dopamine into vesicles, leading to the generation of reactive oxygen species in the cytoplasm, is a key event in the demise of dopaminergic neurons in Parkinson's disease, and might represent a common pathway that underlies both genetic and sporadic forms of the disorder