Biology subjects

D'Errico, A.

Publications and source records attributed to D'Errico, A..

4 recordsLinked to original sources

bioRxiv2026

Vascular signals coordinate cerebellar circuitry development

Neural circuit assembly requires precise coordinated interactions between developing neurons and the vasculature, yet the instructive signals provided by endothelial cells remain largely unknown. Here, we identify a vascular-to-neural signaling axis that orchestrates postnatal cerebellar development. Endothelial-specific deletion of the adaptor protein Dab1 in mice disrupted vascular patterning and uncoupled the growth of major cerebellar neuronal populations. We show that endothelial Dab1 in the cerebellum drives secretion of the morphogen Wnt5a, which acts through Frizzled-2 to restrain granule-cell progenitor proliferation and promote Purkinje-cell dendritic maturation. Endothelial Wnt5a deletion phenocopied Dab1 endothelial mutant (Dab1i{Delta}EC) defects, whereas exogenous Wnt5a restored normal progenitor dynamics in Dab1i{Delta}EC cerebellar slices, demonstrating pathway sufficiency. Functionally, loss of this vascular signal impaired Purkinje-cell firing, diminished parallel-fiber input, reduced synapse formation from both parallel and climbing fibers, and disrupted long-term plasticity. These findings reveal a key instructive role for blood vessels in shaping cerebellar architecture and establishing functional circuit connectivity.

neuroscience↗

bioRxiv2025

Effects of Polyphenolic Extracts from Mediterranean Forage Crops on Cholinesterases and Amyloid Aggregation Relevant to Neurodegenerative Diseases

Alzheimers and Parkinsons diseases are the most common neurodegenerative disorders of the central nervous system, characterized by progressive neuronal death and neurological dysfunction. There is currently no treatment that effectively slows the disease progression, and the synthetic drugs proposed to alleviate the symptoms, often cause side effects. Many studies are now focused on neuroprotective properties exhibited by natural agents, such as polyphenols, whose action on different cell signaling pathways is well known. In this article, we analyzed the composition and the properties of polyphenolic extracts from forage plants, such as Lotus ornitopoidioides, Hedysarum coronarium L., Medicago sativa and Cichorium intybus. The LC-MS/MS analysis on the extracts allowed the identification of total 24 phenolic acids and 25 flavonoids. The effects of the extracts on key enzymes of cholinergic neurotransmission, such as acetyl cholinesterase and butyryl cholinesterase, was examined, together with an investigation on the aggregation and disaggregation of amyloid fibrils. The polyphenols acted as inhibitors of the considered enzymes, and interfered with the amyloidogenesis process, with differences depending on the specific extracts. The inhibition constants towards cholinesterases ranged in the 60 - 240 {micro}M interval; the extracts showed different inhibition mechanisms, from competitive to non-competitive. Differences also emerged in the amyloidogenesis process, with IC50 values comprised in a large interval. Finally, the extract from M. sativa significantly reduced the cell viability of the human neuroblastoma cell line SH-SY5Y. These results suggest that polyphenols extracted from these plants may behave as multitargeting agents against key factors of Alzheimers and Parkinsons diseases. Therefore, they can be considered as promising candidates for the prevention and management of symptoms of these neurodegenerative disorders in combination with pharmacological therapies.

biochemistry↗

bioRxiv2021

Molecular diagnosis and prognosis of cancers of unknown-primary (CUPs): progress from a microRNA-based droplet digital PCR assay

Metastasis is responsible for the majority of cancer-related deaths. Particularly challenging is the management of metastatic cancer of unknown primary site (CUP), whose tissue-of-origin (TOO) remains undetermined even after expensive investigations. CUP therapy is rather unspecific and poorly effective. Molecular approaches developed to identify CUPs potential tissue-of-origin, can overcome some of these issues. In this study, we applied a pre-determined set of microRNAs (miRNAs) to infer the TOO of 53 metastatic cancers of unknown or uncertain origin. We designed a molecular assay to quantify 89 miRNAs at the copy number level, using EvaGreen-based Droplet Digital PCR. We assessed miRNA expression in 159 samples including primary tumors from 17 tumor classes (reference set), metastases of known and unknown origin. We applied two different statistical models for class prediction to obtain CUPs most probable TOOs. Specifically, we used the shrunken centroids using PAMR (Prediction Analysis of Microarrays for R) and the least absolute shrinkage and selection operator (LASSO) models. The molecular test was successfully applied to FFPE samples and provided a site-of-origin identification within one-week from the biopsy procedure. The most frequently predicted origins were gastrointestinal, pancreas, breast and lung. The assay was applied to multiple metastases from the same CUP, collected from different metastatic sites: the molecular prediction revealed an impressive agreement in site-of-origin prediction, intrinsically validating our assay. The final prediction was compared with the clinico-pathological hypothesis of primary site. Moreover, a panel of 14 miRNAs proved to have prognostic value and being associated with overall survival. Our study demonstrated that miRNA expression profiling in CUP samples could be employed as diagnostic and prognostic test. Our molecular analysis can be performed on-request, concomitantly with standard diagnostic workup and in association with genetic profiling, to offer valuable indication about the possible primary site, thereby supporting treatment decisions.

pathology↗

bioRxiv2018

Histological evidences of diabetic kidney disease precede clinical diagnosis

In the absence of a histhological diagnosis, persistent albuminuria is globally accepted as the main diagnostic criteria for diabetic kidney disease.\n\nIn the present retrospective study, we evaluated data from an Italian cohort of 42 diabetic deceased donors (mainly type 2 diabetes). Using kidney biopsies obtained at time of donation to evaluate single or double allocation based on Karpinski score, we determined the prevalence of histological lesions attributable to diabetes.\n\nAll 42 donors presented with normoalbuminuria and an estimated Glomerular Filtration Rate (CKD-EPI) > 60 ml/min/1.73m2. Of the 36 patients with available kidney biopsy, one was non interpretable and 32 had histopathological lesions consistent with diabetic kidney disease and encompassing all histological classes.\n\nThus, we found a relatively high proportion of histologically proven diabetic kidney disease that was clinically undiagnosed as none of the patient had significant albuminuria and eGFR <60 cc/min/1.73 m2. Our data support the need to implement routine kidney biopsies in normoalbuminuric diabetic subjects in early stages of Chronic Kidney Disease. As others have shown that histological lesions associated with diabetic kidney disease predict disease progression, such strategy may help to risk stratify patients and may guide therapeutic decisions at early disease stages.

scientific communication and education↗