Adoptive cell therapy with macrophage-drug conjugates facilitates cytotoxic drug transfer and immune activation in glioblastoma models.

The treatment of solid tumors faces substantial hurdles because of inadequate drug delivery and the immunosuppressive tumor microenvironment. To address these challenges, we developed a therapeutic platform using macrophages loaded with ferritin-drug conjugates, referred to as macrophage-drug conjugates (MDC), and applied it to glioblastoma, an immunologically cold solid tumor. MDC loaded with ferritin-conjugated monomethyl auristatin E enabled efficient, cell contact-dependent transfer of the payload by a mechanism involving transfer of iron-binding proteins, from either mouse or human macrophages preferentially into glioma cells.

MAP4 kinase-regulated reduced CLSTN1 expression in medulloblastoma is associated with increased invasiveness.

De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB. Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling.

Degeneration of ipRGCs in Mouse Models of Huntington's Disease Disrupts Non-Image-Forming Behaviors Before Motor Impairment.

Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are photosensitive neurons in the retina and are essential for non-image-forming functions, circadian photoentrainment, and pupillary light reflexes. Five subtypes of ipRGCs (M1-M5) have been identified in mice. Although ipRGCs are spared in several forms of inherited blindness, they are affected in Alzheimer's disease and aging, which are associated with impaired circadian rhythms.

Targeting ENT1 and adenosine tone for the treatment of Huntington's disease.

Huntington's disease (HD) is caused by an abnormal CAG expansion in the exon 1 of huntingtin gene. The treatment of HD is an unmet medical need. Given the important role of adenosine in modulating brain activity, in this study, levels of adenosine and adenine nucleotides in the cerebral spinal fluid of patients with HD and in the brain of two mouse models of HD (R6/2 and Hdh150Q) were analysed.

Type VI adenylyl cyclase negatively regulates GluN2B-mediated LTD and spatial reversal learning.

The calcium-sensitive type VI adenylyl cyclase (AC6) is a membrane-bound adenylyl cyclase (AC) that converts ATP to cAMP under stimulation. It is a calcium-inhibited AC and integrates negative inputs from Ca(2+) and multiple other signals to regulate the intracellular cAMP level. In the present study, we demonstrate that AC6 functions upstream of CREB and negatively controls neuronal plasticity in the hippocampus.

Lack of type VI adenylyl cyclase (AC6) leads to abnormal sympathetic tone in neonatal mice.

Visceral functions are regulated by a basal sympathetic nerve discharge (SND), also known as 'sympathetic tone'. We demonstrate herein that AC6 existed in tyrosine hydroxylase-positive rostral ventrolateral medulla neurons in the brainstem. Adenylyl cyclase (AC) assays showed lower basal and pituitary adenylate cyclase-activating peptide-evoked AC activities in the brainstem of AC6-null mice, indicating that AC6 is a prominent AC isozyme in the brainstem.