New research suggests that most Alzheimer’s cases may rely on the influence of just one gene.

In this study, we identified the aminopeptidase CD13 as a key mediator in a subset of human BrMs originating from breast and lung cancers, with approximately 30% of samples exhibiting cancer cell-specific CD13 expression. Notably, this prevalence aligns with previous reports in breast and lung primary tumors. In BC, CD13 cancer cell expression was documented in 36% of patient samples analyzed, with higher rates in invasive ductal carcinoma,³¹ while in lung cancer, 35% of patients analyzed were positive for cancer cell CD13 expression.³² These observations suggest that CD13 expression is maintained during metastatic progression to the brain, underscoring its potential as a therapeutic target. Importantly, CD13 expression in primary lung cancer is associated with significantly reduced survival, with a similar trend in BC.^31,32 Consistent with these data, we show here that patients with HER2+ BC with CD13^high tumors have significantly poorer clinical outcomes. These findings emphasize the importance of stratifying patients by CD13 status to better assess both its prognostic significance and therapeutic potential.

To gain mechanistic insight into CD13 function, we employed murine BrM models from three primary origins (breast, lung, and melanoma) that recapitulate distinct stages of the metastatic cascade. Notably, only the breast-BrM model exhibited robust CD13 expression, suggesting that lung cancer and melanoma may rely on alternative, CD13-independent mechanisms to colonize the brain. CD13 knockdown in breast-BrM cells significantly prolonged survival and reduced metastatic seeding following intracardiac injection. This effect was less pronounced when cancer cells were introduced directly into the brain parenchyma (intracranial injection) or implanted at the primary site (MFP), underscoring CD13’s predominant role during the initial colonization phase of metastasis.

Both gain-and loss-of-function experiments confirmed CD13’s functional importance in metastatic seeding. CD13 has been described as a moonlighting enzyme with diverse cellular functions relevant to regulating metastasis,^16,17 including β1 integrin recycling,²¹ cell migration,²¹ and activation of the MAPK and PI3K pathways.³³ Based on our RNA-seq analysis, CD13 overexpression may further enhance metastatic efficiency through activation of Rho family GTPases and effectors that orchestrate cytoskeletal remodeling, endothelial cell adhesion, and transendothelial migration.³⁴ These features position CD13 as a compelling anti-cancer target; indeed, CD13 inhibition has been explored in several therapeutic development efforts. However, no brain-permeable CD13 inhibitor has yet been approved worldwide for clinical use,¹⁶ representing a critical gap in the translational landscape.

How neuronal function is shaped by mitochondria.

Despite the established links between mitochondrial dysfunction and neuronal disorders, the specialization of mitochondria to support the specific demands of neurons has been less extensively explored.

Proper mitochondrial positioning influences an array of neuronal functions and processes, from neurodevelopment through synaptic transmission, due to the participation of mitochondria as local ATP suppliers, Ca2+ sinks, and sites of neurotransmitter synthesis.

In neurons, mitochondria are also crucial for local translation in axons and dendrites, to which they provide both local ATP and mRNA transport. In this way, mitochondria emerge as centers for neuronal plasticity sciencenewshighlights ScienceMission https://sciencemission.com/Mitochondrial-specialization

Neurons are specialized cells designed to process information and transmit it, often across long distances. In many neurons, the axonal volume far exceeds the somato-dendritic volume, creating a need for long-range transport and local polarization mechanisms. In addition, action potential firing and restoration of ionic gradients, as well as dynamic changes in synaptic plasticity, further increase the energetic demands of neurons. In this review, we highlight the roles mitochondria play in vertebrate neuronal biology and how mitochondrial functionality is tuned to support the unique demands of neurons. We cover the influence of mitochondrial positioning, ATP generation and Ca2+ buffering on neuronal function, and explore the role of mitochondria in neurotransmitter metabolism and local protein translation.