Evidence map›Paper›PMID 40047257›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Genetic and pharmacologic enhancement of SUMO2 conjugation prevents and reverses cognitive impairment and synaptotoxicity in a preclinical model of Alzheimer's disease.

Luana Fioriti, Nadeeja Wijesekara, Elentina K Argyrousi, Shinsuke Matsuzaki, Hironori Takamura, Kanayo Satoh, Kyung Han, Hiroto Yamauchi, Agnieszka Staniszewski, Erica Acquarone and 5 more

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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Luana FioritiDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, MI, Italy.
Nadeeja WijesekaraTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Elentina K ArgyrousiDepartment of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Shinsuke MatsuzakiDepartment of Radiological Sciences, Faculty of Medical Science Technology, Morinomiya University of Medical Sciences, Suminoe Ward, Osaka, Japan.
Hironori TakamuraTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Kanayo SatohTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Kyung HanTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Hiroto YamauchiMINCL, Morinomiya University of Medical Sciences, Suminoe Ward, Osaka, Japan.
Agnieszka StaniszewskiDepartment of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Erica AcquaroneDepartment of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Franca OrsiniDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, MI, Italy.
Annacarla MartucciDepartment of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, MI, Italy.
Taiichi KatayamaDepartment of Child Development & Molecular Brain Science, United Graduate School of Child Development, Osaka University, Suita, Osaka, Japan.
Ottavio ArancioDepartment of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Paul E FraserTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.

Funding

SUMOylation and Amyloid-beta elevationR01NS049442 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARANCIO, OTTAVIO · 2005 to 2015
$4.1M
The Role of SUMOylation in Tau-Mediated PathologyR01NS110024 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARANCIO, OTTAVIO · 2019 to 2023
$2.0M
Role of SUMOylation in Mitochondrial/Synaptic Axis Dysfunction Induced by Abnormal Tau in FTDR01NS134902 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FIORITI, LUANA, QUINZII, CATARINA M. · 2023 to 2024
$1.4M
Alzheimer's Association AARG 17-505136 to L.FCIHR PJT-173497Fostering Joint International Research 17KK0197 to S.MGrant-in-Aid for Scientific Research 21K06759 to S.MJapanese Society for the Promotion of ScienceJapanese Society for the Promotion of Science (JSPS)NIH HHS NIH-NINDS R01NS110024NIH HHS NIH R01NS134902 to L.FNIH HHS R01NS049442 to O.ANINDS NIH HHS R01 NS049442NINDS NIH HHS R01 NS110024NINDS NIH HHS R01 NS134902Weston Brain Institute TR192065
6 · The paper itself

Abstract

introductionAmyloid beta oligomers (Aβos) are toxic to synapses and key to the progression of Alzheimer's disease (AD) and amyloid pathology, representing a target for therapeutic strategies.

methodsAmyloid and small ubiquitin modifier 2 (SUMO2) transgenics were analyzed by electrophysiology and behavioral testing. A recombinant analogue of SUMO2, SBT02, was generated and assessed for brain penetration and the ability to mitigate amyloid pathology.

resultsElevated SUMO2 expression prevents cognitive and synaptic impairment in a mouse model of AD amyloid pathology. Systemic administration of SBT02 resulted in high brain bioavailability and prophylactically halted the progression of AD-associated deficits. SBT02 also restored cognition and synaptic function in late-stage amyloid load. Mechanistically, SUMO2 and SBT02 do not alter amyloid processing or clearance and mitigate synaptotoxicity in the presence of high amyloid loads. DISCUSSION: SBT02 is a promising therapeutic strategy to counteract and reverse the toxic effects of Aβos in AD. HIGHLIGHTS: Genetic overexpression of human SUMO2 prevents the long-term potentiation (LTP) impairments and cognitive deficits in amyloid precursor protein (APP) transgenics without affecting amyloid pathology. A recombinant analogue of human SUMO2, termed SBT02, when administered systemically, displays high brain bioavailability and has no adverse effects at high doses. Prophylactic treatment of APP transgenics with SBT02 prior to the development of amyloid pathology results in the prevention of synaptic and behavioral dysfunction. SBT02 also reverses pre-existing LTP and cognitive impairments when administered to APP transgenics with advanced and severe pathology. SBT02 has no impact on amyloid pathology, indicating a mechanism of action on synaptic resistance to Aβ toxicity.

Indexed as

Alzheimer DiseaseCognitive DysfunctionSmall Ubiquitin-Related Modifier ProteinsSynapsesAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainDisease Models, AnimalHumansLong-Term PotentiationMaleMiceMice, TransgenicAmyloid beta-PeptidesAmyloid beta-Protein PrecursorSmall Ubiquitin-Related Modifier ProteinsSUMO2 protein, humanamyloid transgenic mouse modelbehavioral analysesbiologic therapycognitiondrug developmentelectrophysiologypreclinical testingsmall ubiquitin‐like modifiersSUMOylation

Identifiers

PMID40047257
PMCPMC11883658

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.