{"id":799,"date":"2023-12-12T12:40:33","date_gmt":"2023-12-12T12:40:33","guid":{"rendered":"https:\/\/dev.minervainstitute.fi\/associerad-group-neuronal-signalering\/"},"modified":"2024-11-04T09:53:44","modified_gmt":"2024-11-04T09:53:44","slug":"associerad-group-neuronal-signalering","status":"publish","type":"page","link":"https:\/\/minervainstitute.fi\/sv\/forskningsgrupper\/associerad-group-neuronal-signalering\/","title":{"rendered":"Associerad group: Neuronal signalering"},"content":{"rendered":"

Associerad group: Neuronal signalering<\/h1>\n<\/div>
<\/div><\/div>

Vi studerar grundl\u00e4ggande mekanismer bakom neurodegenerativa sjukdomar och nervcellsskador i hj\u00e4rnan. Vi fokuserar p\u00e5 proteinubiquitination och rollen av mitokondriella och endoplasmatiska retikulum (ER) stressv\u00e4gar samt autofagi i patogenesen och modellerna av hj\u00e4rnsjukdomar, och anv\u00e4nder olika proteomiska och genuttrycksmetoder, cellkultur och djurmodeller av sjukdomar och genetiskt modifierade m\u00f6ss. \u00c4ven om majoriteten av gruppen \u00e4r inhyst i Institutet f\u00f6r biomedicin, Medicinska fakulteten, \u00e4r gruppen aktivt engagerad i forskning vid Minerva. <\/p>\n

USP14 och protein ubiquitination i neurodegenerativa st\u00f6rningar<\/u><\/strong><\/p>\n

St\u00f6rningar i proteinhomeostasen \u00e4r f\u00f6rknippade med sjukdomar som cancer och neurodegenerativa st\u00f6rningar. Det deubiquitinerande enzymet USP14 \u00e4r associerat med proteasomen och p\u00e5verkar proteostasen (Srinivasan et al, 2023). Usp-14 uttrycks i hj\u00e4rnan och vi observerade att Usp-14 minskar mutanta Htt-aggregat (Hyrskyluoto et al, 2014). Usp14 kan ocks\u00e5 p\u00e5verka autofagifl\u00f6det via det autofagiassocierade proteinet LC3B (Srinivasan et al, 2020). Genom att anv\u00e4nda gendeletion av USP14 har vi nyligen uppt\u00e4ckt nya funktioner hos USP14 i cellfysiologi inklusive effekter p\u00e5 mitokondrier och lysosomer som f\u00f6r n\u00e4rvarande unders\u00f6ks. <\/p>\n

CNPY2 i neuroskydd och ER-stress<\/u><\/strong><\/p>\n

Canopy Homolog 2 (CNPY2) \u00e4r ett protein som finns i ER som \u00e4r involverat i cellmobilitet, cancer och lipoproteinmetabolism (Do e al, 2012). \u00d6veruttryck av CNPY2 \u00e4r skyddande medan nedreglering av \u00e4r skadligt f\u00f6r neuroner och CNPY2 kan ge viss f\u00f6rdel vid st\u00f6rningar som k\u00e4nnetecknas av neuronf\u00f6rlust s\u00e5som Huntingtons sjukdom (HD). Vi studerar f\u00f6r n\u00e4rvarande den transgena N171-82Q-musen som en modell f\u00f6r HD med hj\u00e4lp av olika protein- och molekyl\u00e4ra metoder och beteendetester (Stepanova et al, 2023).<\/p>\n<\/div><\/div><\/div>

<\/span><\/div>

Gruppledare<\/h3>\n

Dan Lindholm, MD, professor
\ndan.lindholm@helsinki.fi<\/p>\n<\/div>

Gruppmedlemmar<\/h3>\n

Ove Eriksson, FD
\nMiriana Scordino, MSc
\nChiara Valencia, MSc
\nUrho Kere, medicinstudent<\/p>\n<\/div><\/div><\/div>

LACTB i mitokondriell fysiologi<\/u><\/strong><\/p>\n

LACTB \u00e4r ett mitokondriellt protein mellan membranen som kan polymerisera till membranf\u00e4sta spiralformade filament med likhet med bakteriella penicillinbindande proteiner och beta-laktamaser. LACTB har kopplats till cancer som tum\u00f6rsuppressor och till lipidmetabolism (Cascone et al, 2022), men de exakta fysiologiska funktionerna och m\u00f6jliga substraten f\u00f6r LACTB) \u00e4r ok\u00e4nda. H\u00e4r kommer vi att studera dessa fr\u00e5gor ytterligare inklusive utf\u00f6ra analyser av LACTB knockout-m\u00f6ss.<\/p>\n<\/div><\/div><\/div>

<\/span><\/div>

Gruppledare<\/h3>\n

Dan Lindholm, MD, professor
\ndan.lindholm@helsinki.fi<\/p>\n<\/div>

Gruppmedlemmar<\/h3>\n

Ove Eriksson, FD
\nVignesh Srinivasan, MSc
\nMiriana Scordino, MSc
\nChiara Valencia, MSc
\nUrho Kere, medicinstudent<\/p>\n<\/div><\/div><\/div><\/div><\/div>

Utvalda publikationer<\/h3>\n<\/div>
<\/div><\/div>
Ajoolabady A, Lindholm D, Ren J, <\/span>Pratic\u00f2 D (2022) ER Stress and UPR in Alzheimer’s Disease: Mechanisms, Pathogenesis, Treatment. <\/span>Cell Death Dis. <\/span>13:706.<\/span><\/div>\n
\n

Cascone, A., Lalowski, M., Lindholm, D., & Eriksson, O. (2022). Unveiling the Function of the Mitochondrial Filament-Forming Protein LACTB in Lipid Metabolism and Cancer. <\/span>Cells<\/span>, <\/span>11 <\/span><\/i>(10), 1703.<\/span><\/p>\n<\/div>\n

\n

Do, H. T., Tselykh, T. V., M\u00e4kel\u00e4, J., Ho, T. H., Olkkonen, V. M., Bornhauser, B. C., Korhonen, L., Zelcer, N. & Lindholm, D. (2012) Fibroblast Growth Factor-21 (FGF21) Regulates Low-density Lipoprotein Receptor (LDLR) Levels in Cells via the E3-ubiquitin Ligase Mylip\/Idol and the Canopy2 (Cnpy2)\/Mylip-interacting Saposin-like Protein (Msap). J Biol Chem. 287, 12602-12611<\/p>\n<\/div>\n

\n

Hyrskyluoto A, <\/span>Bruelle C, <\/span>Lundh SH, Do HT, Kivinen J, Rappou E, Reijonen S, Waltimo T, Peters\u00e9n \u00c5, Lindholm D, Korhonen L. (2014) Ubiquitin specific protease-14 reduces cellular aggregates and protects against mutant huntingtin-induced cell degeneration: involvement of the proteasome and ER stress-activated kinase IRE1<\/span>a<\/span>. Hum Mol Genetics <\/span>23, 5928-5939.<\/b><\/span><\/p>\n

Korhonen L, Paul ER, Karin W\u00e5hl\u00e9n K, Haring L, Vasar E, Vaheri A, Lindholm D. (2023) Multivariate analyses of immune markers reveal increases in plasma EN-RAGE in first-episode psychosis patients. Translational Psychiatry, 13(1):326.doi 10.1038\/s41398-023-02627-8<\/b><\/p>\n

Lindholm D, Korhonen L, Eriksson O, and K\u00f5ks S (2017) Recent Insights into the Role of Unfolded Protein Response in ER stress in Health and Disease. Frontiers in Cell and Dev. Biol., 5:48.<\/p>\n

Pham DD, Bruelle C, Thi Do H, Pajanoja C, Jin C, Srinivasan V, Olkkonen VM, Eriksson O, Jauhiainen M, Lalowski M, Lindholm D. (2019) Caspase-2 and p75 neurotrophin receptor (p75NTR) are involved in the regulation of SREBP and lipid genes in hepatocyte cells. Cell Death Dis. 11;10(7):537.<\/p>\n

Srinivasan V, Bruelle C, Scifo E, Pham DD, Soliymani R, Lalowski M, Lindholm D. (2020) Dynamic interaction of USP14 with the chaperone HSC70 mediates crosstalk between the proteasome, ER signaling and autophagy. iScience 23(1):100790.<\/p>\n

Srinivasan V, Asghar MY, Zafar S, T\u00f6rnquist K, Lindholm D. (2023) Proliferation and migration of ML1 follicular thyroid cancer cells are inhibited by IU1 targeting USP14: role of proteasome and autophagy flux. Front Cell Dev Biol. 11: 30 aug2023.<\/p>\n

Stepanova P, Kumar D, Cavonius K, Korpikoski J, Sirjala J, Lindholm D, Voutilainen MH (2023) Beneficial behavioral effects of cerebral <\/span>dopamine neurotrophic factor (CDNF) infusion in the N171-82Q transgenic model of Huntington\u2019s disease. Scientific Report 13:2953.<\/p>\n<\/div>\n

<\/div>\n<\/div><\/div><\/div><\/div><\/div>

Finansi\u00e4rer av forskningen<\/h3>\n<\/div>
<\/div><\/div>

Doctorandprogrammet i Biomedicin (DPBM)
\nFinska Vetenskaps-Societeten
\nMagnus Ehrnrooths Stiftelse
\nFinska L\u00e4kares\u00e4llskapet
\nMedicinska Underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa r.f.
\nHelsingfors universitet<\/p>\n<\/div><\/div><\/div><\/div><\/div>

F\u00f6lja<\/h3>\n<\/div>
<\/div><\/div>

Research gate: https:\/\/www.researchgate.net\/profile\/Dan-Lindholm<\/a><\/p>\n<\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":878,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"100-width.php","meta":{"footnotes":""},"class_list":["post-799","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/799","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/comments?post=799"}],"version-history":[{"count":6,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/799\/revisions"}],"predecessor-version":[{"id":1514,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/799\/revisions\/1514"}],"up":[{"embeddable":true,"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/pages\/878"}],"wp:attachment":[{"href":"https:\/\/minervainstitute.fi\/sv\/wp-json\/wp\/v2\/media?parent=799"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}