BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences.

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors.

Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.

Lysosomal storage disorders (LSDs) are a large disease class involving lysosomal dysfunction, often resulting in neurodegeneration. Sandhoff disease (SD) is an LSD caused by a deficiency in the β subunit of the β-hexosaminidase enzyme (). Although expression in the brain is specific to microglia, SD primarily affects neurons.

BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences.

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors.

Complement C5a receptor 1 blockade reverses cognitive deficits following cranial radiation therapy for brain cancer.

Cranial radiation therapy (RT) for brain cancers leads to an irreversible decline in cognitive function without an available remedy. Radiation-induced cognitive deficits (RICD) are particularly a pressing problem for the survivors of pediatric and low grade glioma (LGG) patients who often live long post-RT. Radiation-induced elevated neuroinflammation and gliosis, triggered by the detrimental CNS complement cascade, lead to excessive synaptic and cognitive loss.

Immune Checkpoint Inhibition-related Neuroinflammation Disrupts Cognitive Function.

Unlabelled: Combinatorial blockade of Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1) significantly improve the progression-free survival of individuals with metastatic cancers, including melanoma. In addition to unleashing anti-tumor immunity, combination immune checkpoint inhibition (ICI) disrupts immune-regulatory networks critical for maintaining homeostasis in various tissues, including the central nervous system (CNS). Although ICI- and cancer-related cognitive impairments (CRCI) in survivors are increasingly becoming evident, our understanding of ICI-induced immune-related adverse effects (IREA) in the CNS remains incomplete.

BDNF Augmentation Using Riluzole Reverses Doxorubicin-Induced Decline in Cognitive Function and Neurogenesis.

Cancer-related cognitive impairment (CRCI) considerably affects the quality of life of millions of cancer survivors. Brain-derived neurotrophic factor (BDNF) has been shown to promote survival, differentiation, and maintenance of in vivo dentate neurogenesis, and chemotherapy induces a plethora of physiological and cellular alterations, including a decline in neurogenesis and increased neuroinflammation linked with cognitive impairments. In our clinical studies, breast cancer patients treated with doxorubicin (Adriamycin, ADR) experienced a significant reduction in the blood levels of BDNF that was associated with a higher risk of CRCI.