[autismo-biologia] R: aminoacidi a catena ramificata e autismo

[angsaumbriaonlus a libero.it]

Ciao Daniela 
ti chiedo la possibilità di postare su fb questo tuo messaggio, ovviamente 
epurandolo da nomi e cognomi .
Grazie Paola



>----Messaggio originale----
>Da: daniela a autismo33.it
>Data: 09/12/2016 21.36
>A: <autismo-biologia a autismo33.it>
>Ogg: [autismo-biologia] aminoacidi a catena ramificata e autismo
>
>E’ stato pubblicato il primo dicembre scorso l’articolo
>
> Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of
>Autism Spectrum Disorder
>Dora C. Tărlungeanu  Elena Deliu Christoph P. Dotte Majdi Kara
>Philipp Christoph Janiesch Mariafrancesca Scalise Michele Galluccio Mateja
>Tesulov Emanuela Morelli Fatma Mujgan Sonmez  Kaya Bilguvar Ryuichi Ohgaki
>Yoshikatsu Kanai Anide Johansen Seham Esharif Tawfeg Ben-Omran Meral Topcu
>Avner Schlessinger Cesare Indiveri Kent E. Duncan Ahmet Okay Caglayan
>Murat Gunel Joseph G. Gleeson Gaia Novarino15,
>Cell, Volume 167, Issue 6, p1481–1494.e18, 1 December 2016
>
>http://www.cell.com/cell/fulltext/S0092-8674(16)31534-3
>
>I dati salienti del lavoro di cui l’articolo dá  il resoconto sono i seguenti
>
>- il gene Slc7a5  é critico per mantenere nel cervello livelli normali di
>aminoacidi a    catena ramificata (branched-chain amino acid:  BCAA )
>- un deficit di  BCAA cerebrali innesca nei topi delle anomalie
>neurocomportamentali
>- I pazienti con mutazioni di Slc7a5  hanno disturbi dello spettro
>autistico e ritardi motori
>- il comportamento anomalo del topo mutante per Slc7a5  é parzialmente
>corretto da iniezioni di aminoacidi a catena ramificata.
>
>L’articolo é di grande interessa perché
>- scopre un nuovo gene la cui mutazione é causa di autismo.
>- di questo gene si conosce la funzione (la sua mancanza impedisce
>l’ingresso di  BCAA nel cervello).
>- nel topo adulto si sono avuti miglioramenti del comportamento con la
>somministrazione intracerebrale di  aminoacidi a catena ramificata.
>
>La mutazione associata a spettro autistico  é stata riscontrata in figli
>di coppie consanguinee.
>
>A questo punto si pone il solito quesito.   Se si trovasse una terapia
>efficace e praticabile nell’uomo, é  plausibile pensare che la stessa
>terapia funzionerebbe anche in altre condizioni, oltre che nella mutazione
>di  Slc7a5?
>
>Ho posto la domanda ad una coautrice del lavoro, Gaia Novarino, che mi ha
>inviato la seguente risposta
>
>Gentile Daniela,
>     grazie per il suo interesse nella nostra ricerca.
>
>Per quanto riguarda la sua domanda rispetto al gruppo più’ ampio di
>soggetti, la nostra ipotesi e’ che benché’ ci siano molte diverse
>mutazioni genetiche che causano disturbi dell spettro autistico e altre
>malattie del neurosviluppo, in diversi casi pensiamo sia possibile trovare
>delle analogie funzionali e che quindi soggetti con mutazioni in geni
>diversi potrebbero presentare lo stesso meccanismo patofisiologico. Per
>esempio qualche anno fa abbiamo individuato pazienti con mutazioni in un
>altro gene (BCKDK) che causa ASD. Il meccanismo che conduce all’autismo in
>questi pazienti ipotizziamo sia esattamente lo stesso di quello di
>pazienti che hanno mutazioni in questo nuovo gene (SLC7A5). Inoltre i dati
>che stiamo acquisendo ci fanno ritenere di poter trovare analogie con
>forme di autismo dovute ad altre mutazioni genetiche ma con un simile
>meccanismo di azione.
>Rimango a vostra disposizione nel caso vi interessasse avere altre
>informazioni.
>Cordiali Saluti,
>
>Gaia
>
>Gaia Novarino, PhD
>Assistant Professor
>Institute of Science and Technology Austria
>Am Campus 1
>A-3400 Klosterneuburg
>Ph.0043224390005901
>gaia.novarino a ist.ac.at
>
>
>Ed ecco il comunicato stampa dell’Institute of Science and Technology (IST
>Austria)
>
>Klosterneuburg, November 30, 2016
>
>New form of autism found
>
>An international team of researchers led by scientists at IST Austria
>identified a new
>form of syndromic autism • Study published in Cell
>Autism spectrum disorders affect around one percent of the world’s
>population and are characterized by a range of difficulties in social
>interaction and communication. In a new study published in Cell today, a
>team of researchers led by Gaia Novarino, Professor at IST Austria, has
>identified a new genetic cause of ASD. Gaia Novarino explains why this
>finding is significant: “There are many different genetic mutations
>causing autism, and they are all very rare. This heterogeneity makes it
>difficult to develop effective treatments. Our analysis not only revealed
>a new autism-linked gene, but also identified the mechanism by which its
>mutation causes autism. Excitingly, mutations in other genes share the
>same autism-causing mechanism, indicating that we may have underscored a
>subgroup of ASDs.”
>“The identification of novel genes, especially in heterogeneous diseases
>such as autism, is difficult. However, as result of a collaborative
>effort, we were able to identify mutations in a gene called SLC7A5 in
>several patients born to consanguineous marriages and diagnosed with
>syndromic autism”, points out Dr. Caglayan, Chairman of the Department of
>Medical Genetics in the School of Medicine at İstanbul Bilim University
>in Turkey and co-author of the study.
>SLC7A5 transports a certain type of amino acids, the so-called
>branched-chain amino acids (BCAA), into the brain. To understand how
>mutations of SLC7A5 lead to autism, the researchers studied mice in which
>SLC7A5 is removed at the barrier between the blood and the brain. This
>reduces the levels of BCAAs in their brain, and interferes with protein
>synthesis in neurons. Consequently, the mice show reduced social
>interaction and other changes in their behavior, which are also observed
>in other autism mouse models. In a previous study, Gaia Novarino and
>colleagues identified a mutation in a gene that is involved in the
>breakdown of these same amino acids in several patients with ASD,
>intellectual
>disability and epilepsy. “Of course, not all genes causing autism affect
>amino acid levels, and these forms of autism are unarguably very rare, but
>it is possible that even more autism- causing genes fall in this group.”
>explains Gaia Novarino.
>Notably, the researchers were able to treat some of the neurological
>abnormalities in the adult mice missing SLC7A5 at the blood-brain barrier.
>After delivering BCAAs straight into the mice’s brains for three weeks,
>the authors observed an improvement in behavioral symptoms. Dora
>Tarlungeanu, PhD student in Gaia Novarino’s group and first author of the
>study, is excited about the outlook this result gives: “Our research found
>a potential treatment for certain symptoms presented in this form of ASD
>in mice but translation into a treatment for ASD patients will require
>many years of additional research.” The researchers’ results contrast with
>the idea that ASDs are always irreversible conditions. The way they
>treated symptoms in the mice can, of course, not directly be used in
>humans. But they show that some of the neurological complications
>presented by mice missing Slc7a5 can be rescued, and so it is possible
>that – eventually – patients may be treated as well.
>Image: A healthy blood-brain barrier (left side) where a transporter
>allows certain amino acids into the brain is compared to the case where
>the transporter is missing (right side). When the transporter is present
>the mice actively move around and socially interact with each other. This
>is measured by the scientists by tracking the movements of the mice
>(locomotion pattern in the middle) as well as their positions (map in the
>lower right). When the transporter is absent, the mice move less and tend
>to stay apart (seen as the two separate red dots in the map) demonstrating
>less interest for social contact - a measure of autism-associate behavior.
>Contact:
>Gaia Novarino, PhD
>Assistant Professor
>gaia.novarino a ist.ac.at
>Dr. Elisabeth Guggenberger
>Media Relations Manager
>E-Mail: elisabeth.guggenberger a ist.ac.at Tel: +43 2243 9000 1199
>Mobile: +43 (0)664 88326170
>IST Austria
>The Institute of Science and Technology (IST Austria) is a PhD granting
>research institution located in Klosterneuburg, 18 km from the center of
>Vienna, Austria. Inaugurated in 2009, the Institute is dedicated to basic
>research in the natural and mathematical sciences. IST Austria employs
>professors on a tenure-track system, postdoctoral fellows, and doctoral
>students at its international graduate school. While dedicated to the
>principle of curiosity-driven research, the Institute owns the rights to
>all scientific discoveries and is committed to promote their use. The
>first president of IST Austria is Thomas A. Henzinger, a leading computer
>scientist and former professor at the University of California in
>Berkeley, USA, und der EPFL in Lausanne, Switzerland.
>www.ist.ac.at
>
>
>
>
>
>_______________________________________________
>Lista di discussione autismo-biologia
>autismo-biologia a autismo33.it
>ANGSA (Associazione Nazionale Genitori Soggetti Autistici).
>Fondazione Augusta Pini ed Istituto del Buon Pastore Onlus.
>Per cancellarsi dalla lista inviare un messaggio a: valerio.
mezzogori a autismo33.it