SCOPERTA RUSSA

[andy75]

(ANSA) - MOSCA, 13 NOV - Per i calvi c'e' una speranza piu' concreta delle spesso illusorie promesse pubblicitarie: scienziati russi hanno scoperto il gene che regola la crescita dei capelli, e sono convinti di poter preparare in futuro pomate veramente efficaci per combattere la 'pelata'. I ricercatori del laboratorio per la genetica molecolare di Mosca, guidati dal professor Ievgheni Rogaev, hanno sottoposto a test circa 350.000 persone, scegliendo poi 50 famiglie campione per studiare l'ereditarieta' del fenomeno. Grazie alle moderne tecnologie di identificazione dei geni, sono riusciti a risalire al responsabile dell' 'effetto Kojak'. Si tratta di un gene che si trova nel terzo cromosoma, e regola la crescita della capigliatura per mezzo della secrezione di un particolare lipide. Gli scienziati russi ritengono che quel grasso sia riproducibile in laboratorio, e che possa favorire una pronta ricrescita. Non solo: il lipide regola anche la crescita dei peli, e una variante della pomata miracolosa potrebbe quindi risolvere anche il problema dei peli superlfui. ''Siamo solo all'inizio, ci vorranno molti altri esperimenti - dice Rogaev al quotidiano Izvestia - ma almeno abbiamo delineato la strada da seguire''. (ANSA).

[rebel77]

(ANSA) - MOSCA, 13 NOV - Per i calvi c'e' una speranza piu' concreta delle spesso illusorie promesse pubblicitarie: scienziati russi hanno scoperto il gene che regola la crescita dei capelli, e sono convinti di poter preparare in futuro pomate veramente efficaci per combattere la 'pelata'. I ricercatori del laboratorio per la genetica molecolare di Mosca, guidati dal professor Ievgheni Rogaev, hanno sottoposto a test circa 350.000 persone, scegliendo poi 50 famiglie campione per studiare l'ereditarieta' del fenomeno. Grazie alle moderne tecnologie di identificazione dei geni, sono riusciti a risalire al responsabile dell' 'effetto Kojak'. Si tratta di un gene che si trova nel terzo cromosoma, e regola la crescita della capigliatura per mezzo della secrezione di un particolare lipide. Gli scienziati russi ritengono che quel grasso sia riproducibile in laboratorio, e che possa favorire una pronta ricrescita. Non solo: il lipide regola anche la crescita dei peli, e una variante della pomata miracolosa potrebbe quindi risolvere anche il problema dei peli superlfui. ''Siamo solo all'inizio, ci vorranno molti altri esperimenti - dice Rogaev al quotidiano Izvestia - ma almeno abbiamo delineato la strada da seguire''. (ANSA).

ma non c'e' nessuno che riesce a contattare rogaev io purtroppo non conosco l'inglese e il russo ciao

[beavis]

E cosa vorresti chiedergli?

[rebel77]

E cosa vorresti chiedergli?

a che punto sono con questi studi e se effettivamente potremmo avere prove concrete ciao

[beavis]

Il fatto è ke quì stiamo parlando dei meccanismi del corpo umano che portano alla formazione dei capelli ma non è stato espresso il problema sulla cura dell'AA.

 

 

Per ora quello che è noto è ke dallo studio di individui con rari casi di alopecia si verifica un difetto genetico con una carenza della produzione di un enzima e questo suggerisce ke questa sostanza regoli la produzione dei capelli.

[beavis]

Allora mettiamola così, questa è la mia personale interpretazione:

 

c'hai l'enzima di Rogaev=capelli

 

niente enzima=pelato

 

 

 

 

Questo enzima serve alla cellula matrice "martix dermal papilla" per generare il processo di cheratinizzazione del bulbo.

Modificato 15 Marzo 2007 da beavis

[beavis]

Human Hair Growth Deficiency Is Linked to a Genetic Defect in the Phospholipase Gene LIPH

 

Mammalian hair follicles are self-renewing organs that represent interesting models for the regulation of stem cells. Hair follicles cycle through periods of growth (anagen), involution (catagen), and rest (telogen) before regenerating at the onset of a new anagen growth phase (1–3). Hair follicle stem cells, permanent residents of the stem cell niche called the "bulge," communicate with the underlying dermal papilla cells and proliferate at anagen onset to generate the progenitor matrix cells required for new hair growth (4). The molecules that control morphogenesis and cycling of hair follicles and the mechanisms underlying hair loss are poorly understood. However, genetic studies of rare familial cases of alopecia (hair loss on the scalp) and hypotrichosis (deficiencies of hair growth) have yielded important information about some of the genes controlling hair growth, including human hairless, desmoglein 4 (DSG4), and corneodesmosin (CDSN) (5–7).

 

Previously, we described individuals within the aboriginal Finno-Ugric population of Russia with a genetic form of hair growth deficiency (8, 9). To identify the genetic defect for this condition, we have now studied two ethnic groups of mixed Caucasian and Mongoloid origin living in the Volga-Ural region of Russia (Mari El and Chuvash). The Mari population belongs to the Finno-Ugric linguistic group and the Chuvash population to the Turks linguistic group. The ancestors of the Chuvash population were probably Volga Bulgars, extruded by Mongols from Volga Bulgaria, who settled in the territory occupied by the Mari ancestral populations. We analyzed 50 families with hypotrichosis (14 from Mari and 36 from Chuvash) identified in a genetic epidemiological study of 171,500 Mari individuals and 178,722 Chuvash individuals (see supporting online material).

 

Affected individuals were characterized by deficiencies of hair growth on the scalp and body starting at birth, but showed no other pathologies. The growth of scalp hairs was retarded or arrested, leading to short hair length. Hair loss on the scalp was occasionally seen in children and progressed with age (Fig. 1A and fig. S1). Histopathological analysis revealed abnormal morphology of hair follicles and dystrophy and fragility of the hairs in analyzed individuals (Fig. 1, B to D).

 

 

 

The parents of affected individuals were normal, and the segregation frequency suggested an autosomal-recessive form of inheritance. We conducted primary genotyping in Mari families with a set of STR (simple tandem repeat) markers selected arbitrarily or from loci implicated in hair defects of humans or rodents. This analysis revealed a potential linkage of the disorder to chromosome 3q26-27. Subsequent homozygous mapping in Mari families with known STR markers in this chromosomal region localized the mutant gene to a 2.26-cM interval between D3S1617 and D3S3583 (Fig. 2A and figs. S2 to S4). The mapped interval contained 17 annotated genes, none of which had been previously implicated in hair growth, and some of the genes were excluded by direct mutation analysis of affected individuals. The discovery of shared common STR haplotypes on 3q27 in unrelated affected individuals indicated that the mutation in the two populations likely arose from a common founder. We speculated that an examination of high-density STR maps on mutant chromosomes of individuals that are separated by many generations might critically shorten the genomic interval. We isolated novel STRs and performed genotyping of 17 STR markers overlapping 5 cM between D3S1571 and D3S1262. Maximum two-point logarithm of the odds ratio for linkage (lod) scores were found for two markers, (CA5) (Zmax = 11.98, = 0.00) and D3S1530 (Zmax = 9.09, = 0.00), located near each other. The analysis of shared and recombinant haplotypes in Mari families assigned the mutant gene to the 0.89-cM interval flanked by the D3S3592 and D3S1530 markers (Fig. 2 and fig. S4). By combining these data with the haplotypes in Chuvash families, we localized the gene to a 350-kb region encompassing four protein-coding genes (MAP3K13, TMEM41A, LIPH, and SENP2) (Fig. 2).

 

 

We sequenced the entire coding regions of the MAP3K13, TMEM41A, SENP2, and LIPH genes, including exon-intron junctions, in selected affected individuals and found no disease-associated mutations. We noted, however, that exon 4 of the LIPH gene was not amplified from DNA samples of affected individuals using flanking intronic polymerase chain reaction (PCR) primers. A PCR product derived from LIPH exon 4 was detected in the parents but not in any affected individuals, suggesting that the deletion of exon 4 existed in a heterozygous state in the parents and in a homozygous state in individuals with hypotrichosis.

 

To map the deletion breakpoints, we designed a series of primers in the genomic region between exon 3 and exon 5, generated PCR products of mutant alleles harboring the deletion, and performed direct sequencing. This mapping of breakpoints determined that a 985-bp deletion eliminates exon 4 and flanking intronic sequences. We then examined all families and confirmed this deletion in the homozygous state in affected individuals and in the heterozygous state in their parents (Figs. 2 and 3). The genomic region between exon 3 and exon 5 is unusually densely saturated by SINE (short interspersed nuclear element) repeats dispersed in the human genome (10). Sequencing of PCR products from the deletion and from wild-type alleles predicts that the deletion is a result of unequal recombination between copies of Alu retrotransposons flanking exon 4. The recombination event presumably occurred between highly homologous 5' regions of the two members of distant subfamilies of Alu elements (Fig. 2A).

 

 

 

To determine the frequency of the mutant allele, we tested 2292 chromosomes in population samples collected irrespective of the hypotrichosis phenotype from Volga-Ural and other regions of Russia. As anticipated, we found heterozygous individuals with the LIPH deletion in populations of Chuvash (the mutant allele frequency P = 0.033) and Mari (P = 0.030) origin. No mutant allele was found in other Finno-Ugric populations (Udmurths) or Russian populations from distant geographic regions. The data suggest that there are more than 98,000 heterozygous mutant carriers and 1,500 homozygous affected individuals in populations of Mari and Chuvash descent. The number of mutation carriers in this region may be higher because of the mutant gene flow to other ethnic groups (SOM Text).

 

Deletion of exon 4 does not alter the reading frame of the LIPH gene; however, the deletion eliminates an evolutionarily conserved domain in the predicted protein (Fig. 2 and figs. S6 and S7). The protein product, lipase H (alternatively called mPA-PLA1), has a striking sequence similarity to phospholipases and members of the large triglyceride lipase family. Like all lipases, lipase H contains a putative catalytic amino acid triad: Ser154, Asp178, and His248 (11, 12). Replacement of the amino acid triad residues by site-directed mutagenesis abolishes enzymatic activity of lipases (12–15). The LIPH mutation associated with hypotrichosis deletes the critical Asp178, as well as several other evolutionarily conserved amino acid residues (Fig. 2B and fig. S7).

 

It has been postulated that phospholipases generate lysophosphatidic acids (LPA, 1- or 2-acyl-lysophosphatidic acids) from phospholipids (16, 17). LPA has been described as an extracellular mediator of many biological functions, such as proliferation, antiapoptotic activity, and cytoskeletal organization, and appears to signal through at least five members of a family of G protein–coupled receptors (12, 17–22). Lipase H is highly homologous to lipase I (LIPI) and phosphatidylserine-specific phospholipase A1 (PS-PLA1). These three proteins also share common structures of short lid domains and partially deleted ß9 loop domains that probably determine the specificity of their phospholipase activity in the production of LPA (14, 23) (figs. S7 and S9).

 

To elucidate whether the LIPH gene is expressed in hair follicle development, we analyzed mRNA transcripts isolated from human hair follicles and other tissues. The expression of LIPH, but not LIPI and PS-PLA1, was prominent in hair follicles, including the stem cell–rich bulge region (Fig. 3 and fig. S8). These data further indicate the importance of LIPH in normal hair formation and growth.

 

The physiological function of LIPH has not yet been elucidated. We speculate that intragenic deletion of the LIPH (loss-of-function mutation) abolishes the enzymatic activity of lipase H and diminishes the production of LPA mediators in hair follicles. Such lipid mediators may affect the migration, differentiation, or proliferation of keratinocytes, culminating in arrest of hair growth (fig. S9). However, LPA-independent mechanisms and other activities, for example, intracellular functioning of LIPH, cannot be ruled out. Like age-related hair loss in the general population, the hypotrichosis and alopecia described here are not associated with other pathologies, and they progress with age. The identification of a genetic defect in LIPH suggests that this enzyme regulates hair growth and therefore may be a potential target for the development of a therapeutic agent for the control of hair loss or growth.

[masaik2000]

Human Hair Growth Deficiency Is Linked to a Genetic Defect in the Phospholipase Gene LIPH

 

Mammalian hair follicles are self-renewing organs that represent interesting models for the regulation of stem cells. Hair follicles cycle through periods of growth (anagen), involution (catagen), and rest (telogen) before regenerating .......

 

 

praticamente?

[beavis]

Qualcuno ha detto che è stato trovato il gene responsabile della caduta dei capelli ma questo non è l'oggetto della discussione; l'oggetto è come funziona il derma e quali sono i meccanismi necessari che protano alla generazione dei capelli.

 

La cosa importante e significativa è che si è trovata, identificata una sostanza un enzima che deve essere espressa; obbligatoriamente dove ci sono i capelli sani e questo suggerisce che queste sostanze partecipano alla rigenerazione e produzione dei capelli.

 

L'idea è quella di ricreare in laboratororio le sostanze necessarie per poi essere usate topicamente.

[destroy]

speriamo ke lo facciano il + presto possibile...queste ricerche sono molto lunghe :(

[beavis]

UP!

[depeche]

Ragà....io so' convinto di una cosa...con la mia sfxxx di m.....a quando avrò 60 anni ...e se c'arrivo...ci sarà qualcosa ke funziona...e io mi prentderò la pomata e me la mettero tutta in C......O

 

....scusate lo sfogo..... :(

[tommy1988]

ahahahaha