Biology subjects

Varone, M.

Publications and source records attributed to Varone, M..

3 recordsLinked to original sources

bioRxiv2024

p75NTR modulation by LM11A-31 counteracts oxidative stress and cholesterol dysmetabolism in a rotenone-induced cell model of Parkinson's disease

Neurotrophins play pivotal roles in the development and proper functioning of the nervous system. The effects of these growth factors are mediated through the binding of high-affinity receptors, known as Trks, as well as the low-affinity receptor p75NTR. The latter has the capacity to induce complex signal pathways, as it favors both pro-survival and pro-apoptotic cascades depending on the physiopathological condition. Recent findings have indicated that p75NTR expression is increased in post-mortem Parkinsons disease (PD) brains, and this upregulation is associated with a significant reduction in neuroprotection. Given its double-edged sword nature, p75NTR has recently been identified as a promising therapeutic target to counteract neurodegenerative events. The present study aims to assess the neuroprotective effects of p75NTR modulation in a rotenone-induced neuronal model of PD. To this end, differentiated SH-SY5Y cells were exposed to rotenone to mimic the PD phenotype, and the small molecule LM11A-31 was used to modulate p75NTR activity. The main results revealed that LM11A-31 significantly mitigated the hallmarks of PD, including cell death, neuromorphological aberrations, and -synuclein accumulation. Pharmacological manipulation of p75NTR also reduced oxidative damage by increasing the expression of transcriptional factors that regulate the antioxidant response and by decreasing the expression of the pro-oxidant NADPH-oxidase modulatory subunits. Furthermore, LM11A-31 hampered cholesterol buildup induced by rotenone, normalizing the expression of proteins involved in cholesterol biosynthesis, uptake and intracellular trafficking. Taken together, these findings suggest that p75NTR modulation may represent a novel approach to counteracting PD abnormalities of redox and cholesterol metabolism.

neuroscience↗

bioRxiv2024

Simultaneous silencing of gut nucleases and a vital target gene by adult dsRNA feeding enhances RNAi efficiency and mortality in Ceratitis capitata adults.

Ceratitis capitata, known as Mediterranean fruit fly (Medfly), is a major dipteran pest significantly impacting fruit and vegetable farming. Currently, its control heavily relies mainly on chemical insecticides, which pose health risks and have effects on pollinators. A friendly and species-specific alternative strategy involves providing double-stranded RNA (dsRNA) through feeding to disrupt essential functions in pest insects, which is poorly explored in dipteran species. Previous reports in Orthoptera and Coleoptera species suggested that dsRNA degradation by two specific nucleases in the intestinal lumen is among the major obstacle to feeding-mediated RNAi in insects. In our study, we experimented with three-day adult feeding using a combination of dsRNA molecules that target the expression of the ATPase vital gene and two intestinal dsRNA nucleases. These dsRNA molecules were recently tested separately in two Tephritidae species, showing limited effectiveness [1,2]. In contrast, we observed 79% mortality over seven days, which was associated with a decrease in mRNA levels of the three targeted genes. As expected, we also observed a reduction in dsRNA degradation following RNAi against nucleases. This research illustrates the potential of utilizing molecules as pesticides to achieve mortality rates in Medfly adults by targeting crucial genes and intestinal nucleases. Furthermore, it underscores the importance of exploring RNAi-based approaches for pest management Simple SummaryThe control of insect pest species, mainly belonging to Orthoptera, Hemiptera, and Coleoptera species, can be based on novel emerging species-specific pesticides. These consist of dsRNA molecules delivered by feeding to insect larvae or adults, which suppress vital gene functions by RNA-RNA sequence complementarity and RNA interference. However, fewer studies of dsRNA feeding have been performed in dipteran pest insects. Two studies in Orthoptera and Coleoptera species have shown that suppressing intestinal enzymes degrading external dsRNA can improve insect mortality rates. Ceratitis capitata (Tephritidae), the Mediterranean fruit fly (Medfly), is a major dipteran pest significantly impacting fruit and vegetable farming. Currently, its control heavily relies mainly on chemical insecticides, which pose health risks and have effects on beneficial pollinators. Previous attempts to induce mortality by adult dsRNA-feeding in this and other Tephritidae species, such as Bactrocera tryoni and B. dorsalis, showed some effectiveness, but were often limited. We improved this method by simultaneously silencing two intestinal nucleases and a vital gene. We have found a mix of three dsRNAs able to induce much higher mortality (79%) within one week, following only three days of adult feeding.

genetics↗

bioRxiv2021

Aedes albopictus bionomics in Procida Island, a promising Mediterranean site for the assessment of innovative and community-based integrated pest management methods.

The colonization of Mediterranean Europe and of other temperate regions by Aedes albopictus created in the last decades an unprecedented nuisance problem in highly infested areas, as well as a new public health threat due to the species competence to transmit exotic arboviruses, such as dengue, chikungunya and zika. The Sterile Insect Technique (SIT) and the Incompatible Insect Technique (IIT) are insecticide-free mosquito-control methods relying on mass release of irradiated/manipulated males which are believed to have a potential in complementing existing and only partially effective control tools. Testing and implementing these approaches are challenging and selection of study sites is an instrumental and crucial step. We carried out a 4-year study in Procida Island (Gulf of Naples, Italy) in strict collaboration with local administrators and citizens to estimate: i) the temporal dynamics, spatial distribution, and population size of Ae. albopictus; and ii) the dispersal and survival of irradiated males. Overall, results provide insights on the bionomics of the mosquito in Southern Europe and draw attention to Procida Island as an ideal site to test innovative control programs against Ae. albopictus which may be used in other Mediterranean and temperate areas."

ecology↗