1 Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 12, 459–509 (2016)

2 Dember, L. M. Amyloidosis-associated kidney disease. J. Am. Soc. Nephrol. 17, 3458–3471 (2006)

3 Askanas, V. & Engel, W. K. Sporadic inclusion-body myositis: conformational multifactorial ageing-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tau. Presse Med. 40, e219–e235 (2011)

4 Gauthier, S. et al. Why has therapy development for dementia failed in the last two decades? Alzheimers Dement. 12, 60–64 (2016)

5 Soejitno, A., Tjan, A. & Purwata, T. E. Alzheimer’s disease: lessons learned from amyloidocentric clinical trials. CNS Drugs 29, 487–502 (2015)

6 Herrup, K. et al. Beyond amyloid: getting real about non-amyloid targets in Alzheimer’s disease. Alzheimers Dement. 9, 452–458 (2013)

7 Selfridge, J. E., E, L., Lu, J. & Swerdlow, R. H. Role of mitochondrial homeostasis and dynamics in Alzheimer’s disease. Neurobiol. Dis. 51, 3–12 (2013)

8 Pellegrino, M. W. & Haynes, C. M. Mitophagy and the mitochondrial unfolded protein response in neurodegeneration and bacterial infection. BMC Biol. 13, 22 (2015)

9 Beck, J. S., Mufson, E. J. & Counts, S. E. Evidence for mitochondrial UPR gene activation in familial and sporadic Alzheimer’s disease. Curr. Alzheimer Res. 13, 610–614 (2016)

10 Mufson, E. J. et al. Mild cognitive impairment: pathology and mechanisms. Acta Neuropathol. 123, 13–30 (2012)

11 Oddo, S. et al. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39, 409–421 (2003)

12 Jovaisaite, V., Mouchiroud, L. & Auwerx, J. The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J. Exp. Biol. 217, 137–143 (2014)

13 Cohen, E., Bieschke, J., Perciavalle, R. M., Kelly, J. W. & Dillin, A. Opposing activities protect against age-onset proteotoxicity. Science 313, 1604–1610 (2006)

14 Link, C. D. C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer’s disease. Exp. Gerontol. 41, 1007–1013 (2006)

15 McColl, G. et al. Utility of an improved model of amyloid-beta (Aβ1–42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer’s disease. Mol. Neurodegener. 7, 57 (2012)

16 Mouchiroud, L. et al. The movement tracker: a flexible system for automated movement analysis in invertebrate model organisms. Curr. Protoc. Neurosci. 77, 8.37.1–8.37.21 (2016)

17 Nargund, A. M., Fiorese, C. J., Pellegrino, M. W., Deng, P. & Haynes, C. M. Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPRmt. Mol. Cell 58, 123–133 (2015)

18 Nargund, A. M., Pellegrino, M. W., Fiorese, C. J., Baker, B. M. & Haynes, C. M. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337, 587–590 (2012)

19 Prahlad, V. & Morimoto, R. I. Integrating the stress response: lessons for neurodegenerative diseases from C. elegans. Trends Cell Biol. 19, 52–61 (2009)

20 Benedetti, C., Haynes, C. M., Yang, Y., Harding, H. P. & Ron, D. Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response. Genetics 174, 229–239 (2006)

21 Wong, A., Boutis, P. & Hekimi, S. Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics 139, 1247–1259 (1995)

22 Yang, W. & Hekimi, S. Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell 9, 433–447 (2010)

23 Houtkooper, R. H. et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature 497, 451–457 (2013)

24 Moullan, N. et al. Tetracyclines disturb mitochondrial function across eukaryotic models: a call for caution in biomedical research. Cell Rep. 10, 1681–1691 (2015)

25 Zheng, L. et al. Macroautophagy-generated increase of lysosomal amyloid β-protein mediates oxidant-induced apoptosis of cultured neuroblastoma cells. Autophagy 7, 1528–1545 (2011)

26 Forloni, G., Colombo, L., Girola, L., Tagliavini, F. & Salmona, M. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 487, 404–407 (2001)

27 Costa, R., Speretta, E., Crowther, D. C. & Cardoso, I. Testing the therapeutic potential of doxycycline in a Drosophila melanogaster model of Alzheimer disease. J. Biol. Chem. 286, 41647–41655 (2011)

28 Loeb, M. B. et al. A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer’s disease. J. Am. Geriatr. Soc. 52, 381–387 (2004)

29 Quirós, P. M. et al. Multi-omics analysis identifies ATF4 as a key regulator of the mitochondrial stress response in mammals. J. Cell Biol. 216, 2027–2045 (2017)

30 Münch, C. & Harper, J. W. Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation. Nature 534, 710–713 (2016)

31 Bao, X. R. et al. Mitochondrial dysfunction remodels one-carbon metabolism in human cells. eLife 5, e10575 (2016)

32 Sidrauski, C., McGeachy, A. M., Ingolia, N. T. & Walter, P. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. eLife 4, e05033 (2015)

33 Palikaras, K., Lionaki, E. & Tavernarakis, N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature 521, 525–528 (2015)

34 Mouchiroud, L. et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154, 430–441 (2013)

35 Gariani, K. et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology 63, 1190–1204 (2016)

36 Zhang, H. et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352, 1436–1443 (2016)

37 Fang, E. F. et al. NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair. Cell Metab. 24, 566–581 (2016)

38 Corcoran, K. A., Lu, Y., Turner, R. S. & Maren, S. Overexpression of hAPPswe impairs rewarded alternation and contextual fear conditioning in a transgenic mouse model of Alzheimer’s disease. Learn. Mem. 9, 243–252 (2002)

39 Cenini, G., Rüb, C., Bruderek, M. & Voos, W. Amyloid β-peptides interfere with mitochondrial preprotein import competence by a coaggregation process. Mol. Biol. Cell 27, 3257–3272 (2016)

40 Gong, B. et al. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol. Aging 34, 1581–1588 (2013)

41 Martire, S. et al. Bioenergetic impairment in animal and cellular models of Alzheimer’s disease: PARP-1 inhibition rescues metabolic dysfunctions. J. Alzheimers Dis. 54, 307–324 (2016)

42 Kim, H. E. et al. Lipid biosynthesis coordinates a mitochondrial-to-cytosolic stress response. Cell 166, 1539–1552 (2016)

43 Wang, X. & Chen, X. J. A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death. Nature 524, 481–484 (2015)

44 Wrobel, L. et al. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature 524, 485–488 (2015)

45 D’Amico, D., Sorrentino, V. & Auwerx, J. Cytosolic proteostasis networks of the mitochondrial stress response. Trends Biochem. Sci. 42, 712–725 (2017)

46 Tiernan, C. T. et al. Protein homeostasis gene dysregulation in pretangle-bearing nucleus basalis neurons during the progression of Alzheimer’s disease. Neurobiol. Aging 42, 80–90 (2016)

47 Liang, W. S. et al. Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc. Natl Acad. Sci. USA 105, 4441–4446 (2008)

48 Fonte, V. et al. Suppression of in vivo β-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J. Biol. Chem. 283, 784–791 (2008)

49 Kamath, R. S., Martinez-Campos, M., Zipperlen, P., Fraser, A. G. & Ahringer, J. Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol. 2, RESEARCH0002 (2001)

50 Koopman, M. et al. A screening-based platform for the assessment of cellular respiration in Caenorhabditis elegans. Nat. Protoc. 11, 1798–1816 (2016)

51 Counts, S. E., Nadeem, M., Lad, S. P., Wuu, J. & Mufson, E. J. Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment. J. Neuropathol. Exp. Neurol. 65, 592–601 (2006)

52 Greenberg, S. A. et al. Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology 65, 1782–1787 (2005)