extracellular matrix ( ecm ) protein interactions are essential for normal biological processes and when disrupted , they may lead to pathological processes .
the laminin ( lm ) proteins are heterotrimers of alpha , beta and gamma chains .
five - , four - and three -chains give rise to at least 16 different protein isoforms in mammals ( 14 ) .
lm isoforms can drive numerous effects in cells , including cell adhesion , differentiation , proliferation , survival / apoptosis and migration ( 5,6 ) .
all these biological processes require the participation of integrins , the major receptors for ecm proteins .
so far , 11 integrins have been described as lm receptors : 11 , 21 , 22 , 31 , 61 , 64 , 71 , 91 , v3 , v5 and v8 ( 79 ) .
several studies have demonstrated the importance of lms in different types of diseases including cancer , myopathies and neurodegenerative disorders .
these disorders may be inherited as autosomal dominant , autosomal recessive or x - linked traits .
these disorders refer to diseases that affect any part of the peripheral nervous system and muscle .
therefore , the ultimate effect of neuromuscular disorders is on the ability to perform voluntary movements , leading to significant disability of the motor system , resulting in almost complete paralysis . in the past decade
nevertheless , the underlying pathogenetic mechanisms remain largely unclear , limiting the development of targeted therapeutics ( 1013 ) .
micrornas ( mirnas ) constitute an abundant class of non - coding rnas involved in regulating post - transcriptional gene expression , predominantly by translational repression .
these small rnas have been identified in animals , plants and viruses . in humans ,
> 1000 mirna sequences have been found so far ( www.mirbase.org ) ( 14,15 ) . during the past decade , a substantial amount of knowledge has been accumulated regarding the biogenesis of mirnas .
a single mirna may have broad effects on gene expression networks , such as regulating cell lineage specicity , cellular functions or stress response .
the binding of mirnas to the 3-untranslated region to their target mrnas leads to a decrease in the expression of the target proteins and mrna destabilization or degradation ( 14,15 ) .
in fact , levels of mirna inversely correlate with mrna levels and directly alter mrna levels ( 1618 ) .
emerging evidence points to specific mirnas targeting and regulating expression of particular proteins that play key roles in pathogenesis .
disease - related dysregulation in mirna expression indicates roles for mirnas in pathophysiological states including cardiac hypertrophy , muscle dystrophy , hepatitis infection , diabetes , parkinson syndrome , haematological malignancies and other types of cancer .
in fact , mirna expression patterns are presently used to classify various tumours ( 1925 ) .
mirnas are also highly expressed in the brain and have important roles in multiple biological processes such as neuronal differentiation , brain development , synapse formation and plasticity and neurodegeneration ( 2628 ) .
abnormally increased or decreased expression of various mirnas may contribute to the pathophysiology of neurodegenerative diseases and psychiatric disorders .
hence , replacement or inhibition of downregulated or upregulated mirnas , respectively , may be clinically beneficial in the treatment of these disorders ( 20 ) .
recently , data showed that lm isoforms are regulated by mirnas , whose molecular signatures related to lm and neuromuscular disorders were significantly modulated .
furthermore , the regulation by these small rnas might be crucial for lm participation in several diseases such as duchenne muscular dystrophy as well as alzheimer s and parkinson s diseases ( 2937 ) .
thus , it is worthwhile to identify and investigate the functional significance of mirna expression , in particular , its role related to modulation of lm isoforms or their corresponding receptors .
likewise , the identification of regulatory pathways may provide new avenues of investigation for the development of novel therapies .
the interrelationship between lm and mirnas appears to play a crucial role in health and disease . in the first version of this database
, we presented a number of publications demonstrating the importance of lms in general , and in particular , the role of these ecm molecules in the haemopoietic system .
the first version of the lm - database was published in 2011 ( 38 ) . for the lm - database version 2.0 ,
we have extended the original biological information by adding new data concerning lm related to neuromuscular disorders , and mirna expression and regulation .
structurally , the first version of lm - databases main menu is subdivided into different tabs : lms , receptor - binding proteins and other related proteins .
the option to open each tab into a given lm or lm - related molecule has been maintained .
gene expression and  tissue distribution separated by species , comprising homo sapiens , mus musculus and rattus novergicus .
a powerful design feature of the lm - database version 2.0 is the ability to search datasets to explore the biological aspects of lm in neuromuscular disorders and their relationship with mirnas .
the information retrieved from the literature and inserted into this version was manually annotated and curated .
in addition , each record has been linked to a pubmed i d ( pmid ) , which has been directly linked to the corresponding abstract retrieved from pubmed .
neuromuscular disorders tab , arranged in the main menu , and the  mirna  lm relationship tab inserted for each molecule placed in the list of proteins .
the lm - database web site is interlinked with other publicly available databases , e.g. 2d gel , retrieved from uniprot ( 1 ) , protein data bank ( pdb ) ( 2 ) , protein domains in pfam ( 3 ) and interpro ( 4 ) , as well as ensembl ( 5 ) .
this enables users to follow links and retrieve relevant information from other sources related to the biological area of interest .
this tab comprises a collection of information regarding the involvement of lms in neurodegenerative disorders .
infectious neuropathies and  neurodegenerative diseases. when clicking onto a chosen topic , users gain access to annotated information concerning specific groups of neuromuscular disorders . additionally , to facilitate access to data , users can find a number of database links related to brain disorders inside this tab .
altered expression of certain mirnas in the brain of patients with neurodegenerative diseases has been described , and a growing amount of publications have shown that ecm protein expressions are involved in several neuromuscular diseases .
lm  mirna relationship tab . for each lm or lm - related molecule presented in the list of proteins , appropriate
it is important to note that neurodegenerative disease - specific mirna contents were also incorporated in the 
in addition , this tab contains a list of links to a compilation of mirna databases , web sites and servers , which allows users to access the contents of several mirna databank sites .
structurally , the first version of lm - databases main menu is subdivided into different tabs : lms , receptor - binding proteins and other related proteins .
the option to open each tab into a given lm or lm - related molecule has been maintained .
gene expression and  tissue distribution separated by species , comprising homo sapiens , mus musculus and rattus novergicus .
a powerful design feature of the lm - database version 2.0 is the ability to search datasets to explore the biological aspects of lm in neuromuscular disorders and their relationship with mirnas .
the information retrieved from the literature and inserted into this version was manually annotated and curated .
in addition , each record has been linked to a pubmed i d ( pmid ) , which has been directly linked to the corresponding abstract retrieved from pubmed .
neuromuscular disorders tab , arranged in the main menu , and the  mirna  lm relationship tab inserted for each molecule placed in the list of proteins .
the lm - database web site is interlinked with other publicly available databases , e.g. 2d gel , retrieved from uniprot ( 1 ) , protein data bank ( pdb ) ( 2 ) , protein domains in pfam ( 3 ) and interpro ( 4 ) , as well as ensembl ( 5 ) .
this enables users to follow links and retrieve relevant information from other sources related to the biological area of interest .
this tab comprises a collection of information regarding the involvement of lms in neurodegenerative disorders .
infectious neuropathies and  neurodegenerative diseases. when clicking onto a chosen topic , users gain access to annotated information concerning specific groups of neuromuscular disorders . additionally , to facilitate access to data , users can find a number of database links related to brain disorders inside this tab .
altered expression of certain mirnas in the brain of patients with neurodegenerative diseases has been described , and a growing amount of publications have shown that ecm protein expressions are involved in several neuromuscular diseases .
lm  mirna relationship tab . for each lm or lm - related molecule presented in the list of proteins , appropriate
it is important to note that neurodegenerative disease - specific mirna contents were also incorporated in the  neuromuscular disorders tab . in addition
, this tab contains a list of links to a compilation of mirna databases , web sites and servers , which allows users to access the contents of several mirna databank sites .
the lm - database was the first of its kind that collected a substantial amount of data concerning a non - collagenous extracellular protein family .
currently , it is the most comprehensive source of information related to lms , and it provides an overview on lms as well as lm receptor expression in physiology and pathophysiology . we have updated information on lms and integrins related to neuromuscular disorders to lm - database version 2.0 .
considering the prominent role of mirnas in regulating gene expression , it was considered essential to include detailed information concerning mirna expression related to lms and neuromuscular diseases .
this was made possible by the addition of two navigation tabs , which give direct access to current data from the literature .
the amount of available information in lm - database version 2.0 has been largely improved and expanded compared with the first version .
finally , the growing body of publications concerning mirnas related to lms and neuromuscular diseases further highlights the relevance of this database .
overall , we plan to update lm - database continuously with new data from the literature as well as to look for more improvements .
brazilian grant ( pronex ) conjointly provided by conselho nacional de desenvolvimento cientfico e tecnolgico ( cnpq ) and fundao carlos chagas filho de amparo  pesquisa do estado do rio de janeiro ( faperj ) ; other brazilian institutions , including the coordenao de aperfeioamento de pessoal de nivel superior ( capes ) , laboratrio nacional de computao cientfica ( lncc ) and fundao oswaldo cruz ( fiocruz ) , also contributed for funding the project . funding for open access charge : lncc .
 the laminin ( lm)-database , hosted at http://www.lm.lncc.br , was published in the nar database 2011 edition . 
 it was the first database that provided comprehensive information concerning a non - collagenous family of extracellular matrix proteins , the lms . in its first version , 
 this database contained a large amount of information concerning lms related to health and disease , with particular emphasis on the haemopoietic system . 
 users can easily access several tabs for lms and lm - related molecules , as well as lm nomenclatures and direct links to pubmed.the lm - database version 2.0 integrates data from several publications to achieve a more comprehensive knowledge of lms in health and disease . 
 the novel features include the addition of two new tabs ,  
 neuromuscular disorders and  
 mirna-lm relationship. more specifically , in this updated version , an expanding set of data has been displayed concerning the role of lms in neuromuscular and neurodegenerative diseases , as well as the putative involvement of micrornas . given the importance of lms in several biological processes , such as cell adhesion , proliferation , differentiation , migration and cell death , this upgraded version expands for users a panoply of information , regarding complex molecular circuitries that involve lms in health and disease , including neuromuscular and neurodegenerative disorders . 
INTRODUCTION
CHANGES IN LM-DATABASE VERSION 2.0
Updated database contents
Neuromuscular disorders tab
LMmiRNA Relationship tab
CONCLUDING REMARKS
FUNDING