venerdì, Marzo 29, 2024

Synucleinopathy diagnosis is “under the skin”: biopsy as the next generation tool for early detection

Synucleinopathies are neurodegenerative illnesses that cause phosphorylated alpha-synuclein protein...

Il ruolo delle vitamine liposolubili nelle sindromi neuropsichiatriche

Introduzione La salute mentale è una componente integrale ed essenziale...

C3 fuori e dentro le cellule: il nuovo ruolo di un regolatore immunitario nel diabete non è di “complemento”

Sebbene esistano molte differenze tra il diabete di tipo...

A new drug for autism: unravel, unpack, unsilence.

It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism’s characteristic triad of symptoms. Autism has a strong genetic basis, although the genetics of autism are complex; this arises due to interactions among multiple genes, the environment, and epigenetic factors which do not change DNA sequencing but are heritable and influence gene expression. Many genes have been associated with autism through sequencing the genomes of affected individuals and their parents. Nevertheless, many candidate genes have been located, with only small effects attributable to any particular gene. Most loci individually explain less than 1% of cases of autism. Several lines of evidence point to synaptic dysfunction as a cause of autism. Some rare mutations may lead to autism by disrupting some synaptic pathways, such as those involved with cell adhesion. Mostly instead, involve proteins that regulated synapse structure, cell signaling and/or neuronal maturation.

In an article published in the journal Nature Neuroscience, investigators report how low doses of romidepsin – a drug approved in the United States for the treatment of lymphoma – restores gene expression and social deficits are reversed in a murine model of autism. The new study is thought to be the first to demonstrate that it may be possible to alleviate this primary ASD symptom by targeting a large number of genes associated with the disorder. In their study, three days of treatment with low-dose romidepsin reversed social deficits in mice with the deficient SHANK3 gene, which is a known risk factor for ASD. The inversion of social deficits lasted for 3 weeks. The loss of SHANK3 interrupts the NMDA receptor, which helps to regulate emotions and cognition. The interruption caused problems in communication between brain cells and led to social deficits related to ASD. Researchers have shown that romidepsin is able to reverse social deficits by restoring gene function through an epigenetic mechanism.

Epigenetic mechanisms are genetic processes capable of activating and deactivating genes and altering their expression without modifying their underlying DNA code. There are several ways in which epigenetic mechanisms can alter gene expression without changing their DNA. For example, they can silence genes by attaching chemical labels to their DNA. However, the main epigenetic mechanism at work in ASD is the one that remodels the chromatin structure. One of the important findings of the new study is that it may be possible to address a large number of ASD-related genes with just one drug. Romidepsin is a modifier of histones, which are proteins that help organize DNA in the nucleus. The drug dissolves densely packed chromatin: the result is to restore gene expression by making genes more accessible to their regulators. With the help of genome screening, the researchers found that romidepsin restores gene expression in most of the 200 and more genes, which have been “silenced” in the autistic mouse model used in the study.

It is not an immaterial result: if the cause of autism is a genetic defect, only a genetic remedy can correct it. Could rhomidepsin be the starting milestone to pave the way?

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Qi L et al. Nature Neurosci. 2018 Mar 12.

Zhu W et al. Am J Med Genet A. 2018 Feb 9.

Engineer CT et al. Autism Res. 2018 Jan;11(1):59-68. 

Koberstein JN et al. Sci Signal. 2018 Jan 16; 11(513).

Latest

Synucleinopathy diagnosis is “under the skin”: biopsy as the next generation tool for early detection

Synucleinopathies are neurodegenerative illnesses that cause phosphorylated alpha-synuclein protein...

Il ruolo delle vitamine liposolubili nelle sindromi neuropsichiatriche

Introduzione La salute mentale è una componente integrale ed essenziale...

Gli effetti dello iodio sul metabolismo: come agisce, quali aspetti della salute umana può controllare

La sindrome metabolica (MetS), che comprende ipertensione, obesità addominale,...

Newsletter

Don't miss

Synucleinopathy diagnosis is “under the skin”: biopsy as the next generation tool for early detection

Synucleinopathies are neurodegenerative illnesses that cause phosphorylated alpha-synuclein protein...

Il ruolo delle vitamine liposolubili nelle sindromi neuropsichiatriche

Introduzione La salute mentale è una componente integrale ed essenziale...

Gli effetti dello iodio sul metabolismo: come agisce, quali aspetti della salute umana può controllare

La sindrome metabolica (MetS), che comprende ipertensione, obesità addominale,...

Nascosto in “bella vista”: il regolatore IkB-zeta non è solo un inibitore ma un”doppio agente” immunitario

Il nostro sistema immunitario è straordinariamente potente. Assembla rapidamente...
Dott. Gianfrancesco Cormaci
Dott. Gianfrancesco Cormaci
Laurea in Medicina e Chirurgia nel 1998, specialista in Biochimica Clinica dal 2002, ha conseguito dottorato in Neurobiologia nel 2006. Ex-ricercatore, ha trascorso 5 anni negli USA alle dipendenze dell' NIH/NIDA e poi della Johns Hopkins University. Guardia medica presso la casa di Cura Sant'Agata a Catania. In libera professione, si occupa di Medicina Preventiva personalizzata e intolleranze alimentari. Detentore di un brevetto per la fabbricazione di sfarinati gluten-free a partire da regolare farina di grano. Responsabile della sezione R&D della CoFood s.r.l. per la ricerca e sviluppo di nuovi prodotti alimentari, inclusi quelli a fini medici speciali.

Gimme five: MER approach uncover new proteins for breast cancer. Markers or targets?

Although breast cancer is the most prevalent type of cancer affecting women across the world and is associated with substantial morbidity and a significant...

Ovaio policistico: i batteri intestinali come possibile punto di intervento

La sindrome dell'ovaio policistico (PCOS) colpisce circa il 10% delle donne in età fertile, e le cause esatte sono sconosciute, secondo la rete di...

Campagna contro il tabagismo 2018 “Chi non fuma sta una favola”

Il fumo, attivo e passivo, rappresenta uno dei principali fattori di rischio per la salute ed è la principale causa di tumore. I dati...