Juha Laurén

Massachusetts Institute of Technology, Cambridge, Massachusetts, United States

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Publications (17)211.89 Total impact

  • Juha Laurén
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    ABSTRACT: Soluble oligomeric species of amyloid-β (Aβ) peptide are presumed to be drivers of synaptic impairment, and the resulting cognitive dysfunction in Alzheimer's disease. In 2009, cellular prion protein (PrPC) was identified in a genome-wide screen as a high-affinity receptor for Aβ oligomers, and since then, many studies have explored the role of PrPC in Alzheimer's disease. Herein, I systematically assess the current level of target validation for PrPC in Alzheimer's disease and the merits of the identified approaches to therapeutically affect the PrPC:Aβ oligomer-interaction. The interaction of Aβ oligomers with PrPC in mice impairs hippocampal long-term potentiation, memory, and learning in a manner that involves Fyn, tau, and glutamate receptors. Furthermore, PrPC acts to catalyze the formation of certain Aβ oligomeric species in the synapse and may mediate the toxic effects of other β-sheet rich oligomers as well. Therapeutic approaches utilizing soluble PrPC ectodomain or monoclonal antibodies targeting PrPC can at least partially prevent the neurotoxic effects of Aβ oligomers in mice.
    Journal of Alzheimer's disease: JAD 08/2013; 38(2). DOI:10.3233/JAD-130950 · 4.15 Impact Factor
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    ABSTRACT: The LRRTM family proteins have been shown to act as synaptogenic cell adhesion molecules via interaction with presynaptic neurexins and are associated with neuropsychiatric disorders. LRRTM1-knockout mice have subtle morphological deficits in excitatory hippocampal synapses and were suggested to have impaired cognitive function. Here we report that LRRTM1-knockout mice exhibit an extraordinary phenotype of avoiding small enclosures. In the light-dark box, the knockout mice escape to dark through a standard opening as quickly as wild-type littermates but avoid escaping through a small doorway. While all wild-type mice spontaneously enter a small tube, most knockout mice do not. This apparent aversion to enter narrow space may explain other abnormalities such as increased time in open arms in the elevated plus maze and less visits through a tunnel in the IntelliCage. Moreover, LRRTM1-knockout mice show increased social interaction, reduced nest building and MK801-induced locomotion, and slower swim speed but normal water maze learning. Since LRRTM1 is predominantly expressed in thalamus, hippocampus and limbic cortex, specific synaptic defects in those areas presumably cause these behavioral abnormalities.
    Behavioural brain research 10/2012; 238. DOI:10.1016/j.bbr.2012.10.013 · 3.39 Impact Factor
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    ABSTRACT: Neuronal LRRTM3 (leucine-rich repeat transmembrane 3) protein has been reported to promote amyloid-β protein precursor (AβPP) processing and LRRTM3 is a candidate gene in late-onset Alzheimer's disease. To address the role of LRRTM3 in AβPP processing and amyloid-β (Aβ) production in vivo, we analyzed amyloidogenic processing of AβPP in the brains of LRRTM3-deficient mice and transgenic AβPP/PS1 mice with or without LRRTM3. We did not find differences between the genotypes in the levels of Aβ or AβPP C-terminal fragments indicating that LRRTM3 is not an essential regulator of Aβ production in adult mice. Moreover, Aβ levels in primary cortical neurons were similar between the genotypes, indicating that LRRTM3 is not required for Aβ generation in developing mice.
    Journal of Alzheimer's disease: JAD 06/2012; 31(4):759-64. DOI:10.3233/JAD-2012-120193 · 4.15 Impact Factor
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    ABSTRACT: Replying to: H. W. Kessels, L. N. Nguyen, S. Nabavi & R. Malinow 466, 10.1038/nature09217 (2010)Amyloid-beta oligomers are correlated with Alzheimer's disease progression and suppress synaptic plasticity. Through unbiased expression cloning, we identified cellular prion protein (PrP(C)) as an amyloid-beta oligomer binding protein. PrP(C) was necessary for acute amyloid-beta(1-42) (Abeta42) oligomer suppression of synaptic plasticity; thus, it becomes critical to explore the importance of PrP(C) in a range of Alzheimer's-disease-related deficits. Transgenic Alzheimer's disease model mice show deficits of spatial learning and memory, so the most direct assessment of PrP(C) will monitor memory in transgenic Alzheimer's disease model mice deficient for PrP(C). In this paradigm, amyloid-beta species are produced endogenously and the brain is exposed chronically over months. Recently, we have found that deletion of PrP(C) from APPswe/PSen1DeltaE9 transgenic mice restores spatial learning and memory without altering amyloid-beta. Furthermore, the early death, synapse loss and serotonin axonal degeneration of transgenic Alzheimer's disease mice require PrP(C) (ref. 6). Kessels et al. examine PrP(C) in alternative paradigms.
    Nature 08/2010; 466(7308):E4-5. DOI:10.1038/nature09218 · 42.35 Impact Factor
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    ABSTRACT: Soluble oligomers of the amyloid-beta (Abeta) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD). Recently, we reported that synthetic Abeta oligomers bind to cellular prion protein (PrP(C)) and that this interaction is required for suppression of synaptic plasticity in hippocampal slices by oligomeric Abeta peptide. We hypothesized that PrP(C) is essential for the ability of brain-derived Abeta to suppress cognitive function. Here, we crossed familial AD transgenes encoding APPswe and PSen1DeltaE9 into Prnp-/- mice to examine the necessity of PrP(C) for AD-related phenotypes. Neither APP expression nor Abeta level is altered by PrP(C) absence in this transgenic AD model, and astrogliosis is unchanged. However, deletion of PrP(C) expression rescues 5-HT axonal degeneration, loss of synaptic markers, and early death in APPswe/PSen1DeltaE9 transgenic mice. The AD transgenic mice with intact PrP(C) expression exhibit deficits in spatial learning and memory. Mice lacking PrP(C), but containing Abeta plaque derived from APPswe/PSen1DeltaE9 transgenes, show no detectable impairment of spatial learning and memory. Thus, deletion of PrP(C) expression dissociates Abeta accumulation from behavioral impairment in these AD mice, with the cognitive deficits selectively requiring PrP(C).
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 05/2010; 30(18):6367-74. DOI:10.1523/JNEUROSCI.0395-10.2010 · 6.75 Impact Factor
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    ABSTRACT: Delta-Notch signaling is a universal cell-cell communication pathway crucial for numerous developmental and physiological processes. Several proteins interact with and regulate the Notch pathway, including the E3 ubiquitin ligase Neuralized (Neur) that influences the stability and activity of Notch ligands. In mammals there are two homologs of Neur, Neur1 and Neur2, that both can interact with Notch ligands Delta-like1 and Jagged1. Here, we show that Neur2, in contrast to Neur1, is highly expressed during embryonic development of the brain and several non-neural tissues and its mRNA levels subside postnatally. In the hippocampal neurons of the adult brain Neur2 transcripts, in contrast to Neur1, are excluded from the dendrites. Neur2 protein has a predominantly cytoplasmic localization. We also show that in addition to Delta-like1, Neur1 and Neur2 interact with another Notch ligand, Delta-like4.
    Biochemical and Biophysical Research Communications 09/2009; 389(3):420-5. DOI:10.1016/j.bbrc.2009.08.147 · 2.28 Impact Factor
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    Ari Siiriäinen · Oula Seitsonen · Juha Laurén
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    ABSTRACT: During the 1980s, a fairly detailed picture was constructed of the prehistory of the Loita-Mara region, Narok District, southwestern Kenya, up to Elmenteitan times. However, the archaeological sequence after the Elmenteitan period remained poorly understood. Researchers from the University of Helsinki therefore undertook an initial examination of this post-Elmenteitan period in 1984 and 1986. This paper presents results of the work thus undertaken and of the oral histories collected. Field survey in the northeastern Mara Plains identified a host of Pastoral Iron Age (PIA) sites and many late or post-Elmenteitan sites, provisionally named 'Oldorotua' and thought likely to date, based on currently available evidence, to the transition between the Pastoral Neolithic and the Pastoral Iron Age. Two PIA sites were excavated, an iron-smelting/working furnace (GuJe 32) and a few hundred years old boma (GuJf 70). In addition, oral histories were also collected from local informants. Based on these field studies a preliminary culture-historical base sequence for the area is proposed, ranging from Pastoral Neolithic times to the twentieth century. This can be used as a working hypothesis for future research in the area.
    Azania Archaeological Research in Africa 08/2009; 44(2-2):163-193. DOI:10.1080/00671990903047090
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    ABSTRACT: Delineating the molecular basis of synapse development is crucial for understanding brain function. Cocultures of neurons with transfected fibroblasts have demonstrated the synapse-promoting activity of candidate molecules. Here, we performed an unbiased expression screen for synaptogenic proteins in the coculture assay using custom-made cDNA libraries. Reisolation of NGL-3/LRRC4B and neuroligin-2 accounts for a minority of positive clones, indicating that current understanding of mammalian synaptogenic proteins is incomplete. We identify LRRTM1 as a transmembrane protein that induces presynaptic differentiation in contacting axons. All four LRRTM family members exhibit synaptogenic activity, LRRTMs localize to excitatory synapses, and artificially induced clustering of LRRTMs mediates postsynaptic differentiation. We generate LRRTM1(-/-) mice and reveal altered distribution of the vesicular glutamate transporter VGLUT1, confirming an in vivo synaptic function. These results suggest a prevalence of LRR domain proteins in trans-synaptic signaling and provide a cellular basis for the reported linkage of LRRTM1 to handedness and schizophrenia.
    Neuron 04/2009; 61(5):734-49. DOI:10.1016/j.neuron.2009.01.017 · 15.98 Impact Factor
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    ABSTRACT: A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-beta peptide of 40-42 amino acid residues. Prefibrillar, soluble oligomers of amyloid-beta have been recognized to be early and key intermediates in Alzheimer's-disease-related synaptic dysfunction. At nanomolar concentrations, soluble amyloid-beta oligomers block hippocampal long-term potentiation, cause dendritic spine retraction from pyramidal cells and impair rodent spatial memory. Soluble amyloid-beta oligomers have been prepared from chemical syntheses, transfected cell culture supernatants, transgenic mouse brain and human Alzheimer's disease brain. Together, these data imply a high-affinity cell-surface receptor for soluble amyloid-beta oligomers on neurons-one that is central to the pathophysiological process in Alzheimer's disease. Here we identify the cellular prion protein (PrP(C)) as an amyloid-beta-oligomer receptor by expression cloning. Amyloid-beta oligomers bind with nanomolar affinity to PrP(C), but the interaction does not require the infectious PrP(Sc) conformation. Synaptic responsiveness in hippocampal slices from young adult PrP null mice is normal, but the amyloid-beta oligomer blockade of long-term potentiation is absent. Anti-PrP antibodies prevent amyloid-beta-oligomer binding to PrP(C) and rescue synaptic plasticity in hippocampal slices from oligomeric amyloid-beta. Thus, PrP(C) is a mediator of amyloid-beta-oligomer-induced synaptic dysfunction, and PrP(C)-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease.
    Nature 03/2009; 457(7233):1128-32. DOI:10.1038/nature07761 · 42.35 Impact Factor
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    ABSTRACT: In schizophrenia, genetic predisposition has been linked to chromosome 22q11 and myelin-specific genes are misexpressed in schizophrenia. Nogo-66 receptor 1 (NGR or RTN4R) has been considered to be a 22q11 candidate gene for schizophrenia susceptibility because it encodes an axonal protein that mediates myelin inhibition of axonal sprouting. Confirming previous studies, we found that variation at the NGR locus is associated with schizophrenia in a Caucasian case-control analysis, and this association is not attributed to population stratification. Within a limited set of schizophrenia-derived DNA samples, we identified several rare NGR nonconservative coding sequence variants. Neuronal cultures demonstrate that four different schizophrenia-derived NgR1 variants fail to transduce myelin signals into axon inhibition, and function as dominant negatives to disrupt endogenous NgR1. This provides the first evidence that certain disease-derived human NgR1 variants are dysfunctional proteins in vitro. Mice lacking NgR1 protein exhibit reduced working memory function, consistent with a potential endophenotype of schizophrenia. For a restricted subset of individuals diagnosed with schizophrenia, the expression of dysfunctional NGR variants may contribute to increased disease risk.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 01/2009; 28(49):13161-72. DOI:10.1523/JNEUROSCI.3828-08.2008 · 6.75 Impact Factor
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    ABSTRACT: Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.
    Molecular Psychiatry 01/2008; 12(12):1129-39, 1057. DOI:10.1038/sj.mp.4002053 · 15.15 Impact Factor
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    ABSTRACT: In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.
    Nature 08/2007; 448(7149):73-7. DOI:10.1038/nature05957 · 42.35 Impact Factor
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    ABSTRACT: Nogo, MAG, and OMgp are myelin-associated proteins that bind to a neuronal Nogo-66 receptor (NgR/NgR1) to limit axonal regeneration after central nervous system injury. Within Nogo-A, two separate domains are known interact with NgR1. NgR1 is the founding member of the three-member NgR family, whereas Nogo-A (RTN4A) belongs to a four-member reticulon family. Here, we systematically mapped the interactions between these superfamilies, demonstrating novel nanomolar interactions of RTN2 and RTN3 with NgR1. Because RTN3 is expressed in spinal cord white matter, it may have a role in myelin inhibition of axonal growth. Further analysis of the Nogo-A and NgR1 interactions revealed a novel third interaction site between the proteins, suggesting a trivalent Nogo-A interaction with NgR1. We also confirmed here that MAG binds to NgR2, but not to NgR3. Unexpectedly, we found that OMgp interacts with MAG with a higher affinity compared with NgR1. To better define how these multiple structurally distinct ligands bind to NgR1, we examined a series of Ala-substituted NgR1 mutants for ligand binding activity. We found that the core of the binding domain is centered in the middle of the concave surface of the NgR1 leucine-rich repeat domain and surrounded by differentially utilized residues. This detailed knowledge of the molecular interactions between NgR1 and its ligands is imperative when assessing options for development of NgR1-based therapeutics for central nervous system injuries.
    Journal of Biological Chemistry 03/2007; 282(8):5715-25. DOI:10.1074/jbc.M609797200 · 4.57 Impact Factor
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    Molecular Psychiatry 01/2007; 12:1057. DOI:10.1038/sj.mp.4002116 · 15.15 Impact Factor
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    ABSTRACT: The regenerative capacity of the adult mammalian central nervous system is restricted by the myelinating oligodendrocytes that form a nonpermissive environment for axonal growth. Currently only the Nogo receptor (NgR), in complex with p75(NTR) neurotrophin receptor is known to be involved in this inhibitory signalling in neurons. NgR is a common receptor for the three inhibitory myelin proteins Nogo-A, OMgp, and MAG. Here we describe two novel Nogo receptor gene homologs named NGRL2 and NGRL3 from human and mouse that, like NGR, encode putative leucine-rich repeat containing GPI-anchored proteins. We show by in situ hybridisation and by RT-PCR that NGRL mRNAs are predominantly expressed in the neurons of the embryonic and adult central and peripheral nervous systems, and that they together with NGR possess distinct and partially nonoverlapping expression patterns. We also show that all four members of the reticulon family, including Nogo-A, are widely expressed in the nervous system, and therefore are possible ligands for the NgRLs.
    Molecular and Cellular Neuroscience 12/2003; 24(3):581-94. DOI:10.1016/S1044-7431(03)00199-4 · 3.73 Impact Factor
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    ABSTRACT: Leucine-rich repeat containing proteins are involved in protein-protein interactions and they regulate numerous cellular events during nervous system development and disease. Here we have isolated and characterized a new four-membered family of genes from human and mouse, named LRRTMs, that encode putative leucine-rich repeat transmembrane proteins. Human and mouse LRRTMs are highly conserved, and orthologous genes exist in other vertebrates but not in invertebrates. All LRRTMs, except LRRTM4, are located in the introns of different alpha-catenin genes, suggesting coevolution of these two gene families. We show by in situ hybridization and RT-PCR that LRRTM mRNAs are predominantly expressed in the nervous system and that each LRRTM possesses a specific, partially nonoverlapping expression pattern. The structure and expression profile of LRRTM mRNAs suggest that they may have a role in the development and maintenance of the vertebrate nervous system.
    Genomics 05/2003; 81(4):411-21. DOI:10.1016/S0888-7543(03)00030-2 · 2.79 Impact Factor
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    Juha Laurén
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    ABSTRACT: Some leucine-rich repeat (LRR) -containing membrane proteins are known regulators of neuronal growth and synapse formation. In this work I characterize two gene families encoding neuronal LRR membrane proteins, namely the LRRTM (leucine-rich repeat, transmembrane neuronal) and NGR (Nogo-66 receptor) families. I studied LRRTM and NGR family member's mRNA tissue distribution by RT-PCR and by in situ hybridization. Subcellular localization of LRRTM1 protein was studied in neurons and in non-neuronal cells. I discovered that LRRTM and NGR family mRNAs are predominantly expressed in the nervous system, and that each gene possesses a specific expression pattern. I also established that LRRTM and NGR family mRNAs are expressed by neurons, and not by glial cells. Within neurons, LRRTM1 protein is not transported to the plasma membrane; rather it localizes to endoplasmic reticulum. Nogo-A (RTN4), MAG, and OMgp are myelin-associated proteins that bind to NgR1 to limit axonal regeneration after central nervous system injury. To better understand the functions of NgR2 and NgR3, and to explore the possible redundancy in the signaling of myelin inhibitors of neurite growth, I mapped the interactions between NgR family and the known and candidate NgR1 ligands. I identified high-affinity interactions between RTN2-66, RTN3-66 and NgR1. I also demonstrate that Rtn3 mRNA is expressed in the same glial cell population of mouse spinal cord white matter as Nogo-A mRNA, and thus it could have a role in myelin inhibition of axonal growth. To understand how NgR1 interacts with multiple structurally divergent ligands, I aimed first to map in more detail the nature of Nogo-A:NgR1 interactions, and then to systematically map the binding sites of multiple myelin ligands in NgR1 by using a library of NgR1 expression constructs encoding proteins with one or multiple surface residues mutated to alanine. My analysis of the Nogo-A:NgR1 -interactions revealed a novel interaction site between the proteins, suggesting a trivalent Nogo-A:NgR1-interaction. Our analysis also defined a central binding region on the concave side of NgR1's LRR domain that is required for the binding of all known ligands, and a surrounding region critical for binding MAG and OMgp. To better understand the biological role of LRRTMs, I generated Lrrtm1 and Lrrtm3 knock out mice. I show here that reporter genes expressed from the targeted loci can be used for maping the neuronal connections of Lrrtm1 and Lrrtm3 expressing neurons in finer detail. With regard to LRRTM1's role in humans, we found a strong association between a 70 kb-spanning haplotype in the proposed promoter region of LRRTM1 gene and two possibly related phenotypes: left-handedness and schizophrenia. Interestingly, the responsible haplotype was linked to phenotypic variability only when paternally inherited. In summary, I identified two families of neuronal receptor-like proteins, and mapped their expression and certain protein-protein interactions. The identification of a central binding region in NgR1 shared by multiple ligands may facilitate the design and development of small molecule therapeutics blocking binding of all NgR1 ligands. Additionally, the genetic association data suggests that allelic variation upstream of LRRTM1 may play a role in the development of left-right brain asymmetry in humans. Lrrtm1 and Lrrtm3 knock out mice developed as a part of this study will likely be useful for schizophrenia and Alzheimer s disease research. Ihmisen perimässä on noin 23 000 geeniä. Useimpien geenien tehtävät ovat vielä selvittämättä. Neurotieteen alaan kuuluvassa väitöskirjatyössäni kuvaan kaksi ennestään tuntematonta geeniperhettä, jotka yhteensä käsittävät kuusi geeniä. Lisäksi tutkin näiden geenien tehtäviä aivojen kehityksessä ja toiminnassa. Eräänä keskeisenä väitöskirjatyöni tuloksena selvitimme yhteistyössä tri Clyde Francksin (Oxfordin yliopisto, Iso-Britannia) kanssa, että tietty muoto löytämästämme LRRTM1-nimisestä geenistä altistaa vasenkätisyydelle. Tämä löytö on ensimmäinen tunnistettu vasenkätisyyteen liittyvä geenimuutos. Havaitsin myös, että LRRTM1-geeni toimii aktiivisesti niin hiiren kuin ihmisenkin aivoissa jo sikiökaudella. Oletamme, että LRRTM1-geeni ohjaa osaltaan vasemman ja oikean aivopuoliskon kehittymistä toisistaan eroaviksi. Toinen työni päämäärä oli selvittää NGR1-geenin ja kahden tunnistamani NGR1:n kaltaisen geenin tehtäviä. NGR-geeniperhettä koskevat tutkimukseni antavat entistä tarkemman kuvan niistä mekanismeista, jotka rajoittavat hermosäikeiden uudiskasvua esimerkiksi selkäydinvamman tai aivoinfarktin jälkeen. Tiedetään, että hermosolujen pinnalla sijaitsevaan NGR1-reseptoriin sitoutuu useita myeliiniperäisiä hermosolujen kasvua estäviä ligandeja, jotka näin ilmeisesti rajoittavat aivo- ja selkäydinvammoista toipumista. Väitöskirjatyössäni kartoitin systemaattisesti eri ligandien sitoutumista NGR1-reseptoriin. Analyysini osoitti, että NGR1-reseptorin keskiosa on kriittinen kaikkien ligandien sitoutumiselle, ja että sen ympäristössä olevat aminohapot ovat tarpeen vain yksittäisten ligandien sitoutumiselle. Tunnistin myös RTN4-ligandista kolme eri kohtaa, jotka sitoutuvat NGR1:een. Lisäksi osoitin, että RTN2- ja RTN3-proteiinit sitoutuvat NGR1-reseptoriin ja että RTN3-geeni on aktiivinen selkäytimen myeliiniä tuottavissa soluissa; RTN3:n voidaan täten olettaa osallistuvan hermosäikeiden uudiskasvun säätelyyn. Tutkimukseni myös osoittaa, että NGR1:n tavoin NGR2- ja NGR3-geenit ovat erityisen aktiivisia keskushermostossa, mutta kuitenkin niin, että kukin geeni toimii osittain eri aivoalueilla. Osana väitöskirjatyötäni tein kaksi hiirilinjaa, joista toisesta oli poistettu LRRTM1-geeni ja toisesta LRRTM3-geeni. Aiempiin soluviljelmätöihin perustuvat tulokset viittaavat siihen, että LRRTM3-geenillä on keskeinen rooli Alzheimerin tautia aiheuttavan beta-amyloidin tuotannossa. LRRTM3-poistogeeniset hiiret mahdollistavat tämän asian tarkemman tutkimisen. LRRTM1-poistogeenisten hiirten avulla puolestaan voidaan selvittää mekanismeja, jotka johtavat vasemman ja oikean aivopuoliskon välisten erojen kehittymiseen.

Publication Stats

1k Citations
211.89 Total Impact Points

Institutions

  • 2013
    • Massachusetts Institute of Technology
      Cambridge, Massachusetts, United States
  • 2007–2012
    • Yale University
      • Department of Neurology
      New Haven, Connecticut, United States
  • 2003–2009
    • University of Helsinki
      • • Neuroscience Center
      • • Institute of Biotechnology
      Helsinki, Uusimaa, Finland
  • 2007–2008
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States