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

[daniela a autismo33.it]

Tutti i messaggi ad autismo-biologia da me inviati possono essere
divulgati integralmente. Non c'é nulla di privato, per cui non solo non é
necessario, ma é doveroso pubblicare anche nomi e cognomi degli autori
degli articoli citati e commentati. Cordiali saluti e auguri
  Daniela Mariani Cerati


> 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
>>
>>
>>
>>
>>
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