Drug repurposing to target proteostasis and prevent neurodegeneration: Accelerating translational efforts

Brain

Volumn 140, Issue 6, 2017, Pages 1544-1547

  Mercado, Gabriela ^a,b,c   Hetz, Claudio ^a,b,c,d,e  

^a UNIVERSITY OF CHILE   (Chile)

^b UNIVERSITY OF CHILE   (Chile)

^c Universidad de Chile and Geroscience Center for Brain Health and Metabolism   (Chile)

^d BUCK INSTITUTE FOR RESEARCH ON AGING   (United States)

^e HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; GSK 2606414; INITIATION FACTOR 2; INITIATION FACTOR 2ALPHA; MESSENGER RNA; NEUROPROTECTIVE AGENT; PROTEIN INHIBITOR; PROTEIN KINASE R; TUNICAMYCIN; UNCLASSIFIED DRUG;

5' UNTRANSLATED REGION; AMINO ACID METABOLISM; ARTICLE; BLOOD BRAIN BARRIER; DEGENERATIVE DISEASE; DISEASE COURSE; DRUG APPROVAL; DRUG REPOSITIONING; ENDOPLASMIC RETICULUM STRESS; FOOD AND DRUG ADMINISTRATION; HUMAN; NERVE CELL PLASTICITY; NEUROPROTECTION; NONHUMAN; OPEN READING FRAME; PRIORITY JOURNAL; PROTEIN HOMEOSTASIS; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION; UNFOLDED PROTEIN RESPONSE; ANIMAL; MOUSE; PROTEIN PROCESSING; PROTEOMICS;

ANIMALS; DRUG REPOSITIONING; EUKARYOTIC INITIATION FACTOR-2; MICE; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOMICS; PROTEOSTASIS;

EID: 85021927772     PISSN: 00068950     EISSN: 14602156     Source Type: Journal    
DOI: 10.1093/brain/awx107     Document Type: Article

References (10)

1. Halliday M, Radford H, Sekine Y, Moreno J, Verity N, le Quesne J, et al. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis 2015; 6: e1672.
2. Halliday M, et al. Repurposed drugs targeting eIF2a-P-mediated translational repression prevent neurodegeneration in mice. Brain 2017, 104: 1768-83. ID BRAIN-2016-01838.R1.
3. Hetz C, Mollereau B. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat Rev Neurosci 2014; 15: 233-49.
4. Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, et al. Suppression of eIF2alpha kinases alleviates Alzheimer's disease-related plasticity and memory deficits. Nat Neurosci 2013; 16: 1299-305.
5. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Martin MG, et al. Sustained translational repression by eIF2alpha-P mediates prion neurodegeneration. Nature 2012; 485: 507-11.
6. Moreno JA, Halliday M, Molloy C, Radford H, Verity N, Axten JM, et al. Oral treatment targeting the unfolded protein response prevents neurodegeneration and clinical disease in prion-infected mice. Sci Transl Med 2013; 5: 206ra138.
7. Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. The integrated stress response. EMBO Rep 2016; 17: 1374-95.
8. Radford H, Moreno JA, Verity N, Halliday M, Mallucci GR. PERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia. Acta Neuropathol 2015; 130: 633-42.
9. Scheper W, Hoozemans JJ. The unfolded protein response in neurodegenerative diseases: a neuropathological perspective. Acta Neuropathol 2015; 130: 315-31.
10. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife 2013; 2: e00498.