Resveratrol na doença de Alzheimer: uma revisão sobre fisiopatologia e potencial terapêutico

SOUSA, Júlia Canto e; SANTANA, Ana Carolina Fauaze; MAGALHÃES, Gabriela Jesus Prado

doi:10.1590/0004-282X20200010

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View and Review • Arq. Neuro-Psiquiatr. 78 (08) • Ago 2020 • https://doi.org/10.1590/0004-282X20200010 copiar

Resveratrol na doença de Alzheimer: uma revisão sobre fisiopatologia e potencial terapêutico

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

Introdução:

A doença de Alzheimer (DA) é neurodegenerativa e caracterizada por perda progressiva e irreversível da função cognitiva. A presença de placas senis é um dos marcadores patológicos da doença e está associada ao aparecimento de mecanismos neuroinflamatórios. A fisiopatologia exata da DA ainda não é completamente compreendida, e ainda não existem terapias curativas. O resveratrol (3,5,4'-trihidroxi-trans-estilbeno) é um polifenol conhecido por suas propriedades antioxidantes e anti-inflamatórias.

Objetivo:

Revisar o papel do resveratrol nos aspectos fisiopatológicos da DA.

Métodos:

Este estudo realizou uma revisão narrativa da literatura a partir das bases de dados PubMed/Medline, Biblioteca Virtual em Saúde (BVS), Web of Science, SCOPUS e Cochrane Library. Foram incluídos artigos originais, realizados in vitro e in vivo, publicados entre 2008 e 2018.

Resultados:

Foram identificados 667 artigos, dos quais 619 foram excluídos por estarem repetidos ou não se enquadrarem nos critérios de inclusão. O presente estudo inclui os 48 artigos restantes.

Discussão:

O resveratrol demonstra efeitos benéficos e protetores em modelos de DA, bem como parece fornecer uma alternativa terapêutica promissora.

Conclusão:

Embora o resveratrol pareça atenuar alguns aspectos fisiopatológicos da DA, são necessários mais estudos para comprovar a segurança e a eficácia deste composto em seres humanos.

Palavras-chave:
amiloide; sirtuína 1; antioxidantes; polifenóis; nutracêuticos

Compound	Sample	Administration	Results	Reference
Resveratrol, catechins, curcumin and ginkgolides	Aβ42 medium	Added in medium (2, 10 and 100 μM)	Resveratrol inhibited fibrillar formation and aggregation of Aβ42. It did not prevent oligomerization, but it stabilized them, and less toxic oligomers were formed.	Feng et al.²⁶26. Feng Y, Wang X, Yang S, Wang Y, Zhang X, Du X, et al. Resveratrol inhibits beta-amyloid oligomeric cytotoxicity but does not prevent oligomer formation. Neurotoxicology. 2009 Nov;30(6):986-95. https://doi.org/10.1016/j.neuro.2009.08.013 https://doi.org/https://doi.org/10.1016/...
Resveratrol	Tg19959 mice	Supplementation of 300 mg/kg/day for 45 days	Reduced the amount and burden of amyloid plaques in the brain, but it was not statistically significant.	Karuppagounder et al.³³33. Karuppagounder SS, Pinto JT, Xu H, Chen H-L, Beal MF, Gibson GE. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem Int. 2009 Feb;54(2):111-8. https://doi.org/10.1016/j.neuint.2008.10.008 https://doi.org/https://doi.org/10.1016/...
Resveratrol	Aβ structures samples	Added in medium (20 μM)	Remodeled Aβ oligomers into non-toxic oligomers and monomers.	Ladiwala et al.²⁷27. Ladiwala ARA, Lin JC, Bale SS, Marcelino-Cruz AM, Bhattacharya M, Dordick JS, et al. Resveratrol Selectively Remodels Soluble Oligomers and Fibrils of Amyloid Aβ into Off-pathway Conformers. J Biol Chem. 2010 Jul;285(31):24228-37. https://doi.org/10.1074/jbc.M110.133108 https://doi.org/https://doi.org/10.1074/...
Resveratrol	Solution of Aβ and fibrillar Aβ	Added in medium (50 μM)	Bound directly to the monomeric and fibrillar amyloid structure.	Ge et al.¹²12. Ge JF, Qiao JP, Qi CC, Wang CW, Zhou JN. The binding of resveratrol to monomer and fibril amyloid beta. Neurochem Int. 2012 Dec;61(7):1192-201. https://doi.org/10.1016/j.neuint.2012.08.012 https://doi.org/https://doi.org/10.1016/...
Resveratrol	Aβ42 medium	Added in medium (50 μM)	Reduced amyloid aggregation.	Hung et al.³⁰30. Hung VWS, Cheng XR, Li N, Veloso AJ, Kerman K. Electrochemical Detection of Amyloid-Beta Aggregation in the Presence of Resveratrol. J Electrochem Soc. 2013 Apr;160(7):G3097-101. https://doi.org/10.1149/2.014307jes https://doi.org/https://doi.org/10.1149/...
Resveratrol	AβPP/PS1 mice	Supplementation of 174 mg/kg/day for 16 weeks	There was no difference in amyloid burden or tau phosphorylation levels. It increased levels of proteins involved in neuroprotective processes (GSK3 and Transthyretin)	Varamini et al.³⁴34. Varamini B, Sikalidis AK, Bradford KL. Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well as protein levels of drebrin and transthyretin in mice: an exploratory study. Int J Food Sci Nutr. 2014;65(1):89-96. https://doi.org/10.3109/09637486.2013.832171 https://doi.org/https://doi.org/10.3109/...
Resveratrol and EGCG	Aβ42 medium	Added in medium (10:1 molar excess of resveratrol and 4:1 molar excess of EGCG)	Resveratrol and EGCG re-modelled fibrillar conformation of Aβ oligomers into nonfibrillar oligomers and they were no longer cytotoxic	Rushworth et al.²⁸28. Rushworth JV, Griffiths HH, Watt NT, Hooper NM. Prion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem. 2013 Mar;288(13):8935-51. https://doi.org/10.1074/jbc.M112.400358 https://doi.org/https://doi.org/10.1074/...
Resveratrol and curcumin	Aβ42 medium	Added in medium (1:1 molar ratio)	Resveratrol bound to the N-terminus (residue 5-20) of the Aβ42 monomer and caps the height of the oligomers, resulting in a reduction in toxicity	Fu et al.²⁹29. Fu Z, Aucoin D, Ahmed M, Ziliox M, Van Nostrand WE, Smith SO. Capping of Aβ42 Oligomers by Small Molecule Inhibitors. Biochemistry. 2014 Nov;53(50):7893-903. https://doi.org/10.1021/bi500910b https://doi.org/https://doi.org/10.1021/...
Resveratrol and LD55	AβPP/PS1 mice	Supplementation of 100 ppm for 12 months	Decreased Aβ plaque density in brain regions, such as cortex and hippocampus	Solberg et al.²⁰20. Solberg NO, Chamberlin R, Vigil JR, Deck LM, Heidrich JE, Brown DC, et al. Optical and SPION-enhanced MR imaging shows that trans-stilbene inhibitors of NF-κB concomitantly lower Alzheimer’s Disease plaque formation and microglial activation in AβPP/PS-1 transgenic mouse brain. J Alzheimers Dis. 2014 Mar;40(1):191-212. https://doi.org/10.3233/JAD-131031 https://doi.org/https://doi.org/10.3233/...
Resveratrol	Transgenic C. elegans strain CL2006, expressing Aβ1-42	Added in medium (100 μM)	Reduced amyloid aggregation	Regitz et al.³¹31. Regitz C, Fitzenberger E, Mahn FL, Dußling LM, Wenzel U. Resveratrol reduces amyloid-beta (Aβ1-42)-induced paralysis through targeting proteostasis in an Alzheimer model of Caenorhabditis elegans. Eur J Nutr. 2016 Apr;55(2):741-7. https://doi.org/10.1007/s00394-015-0894-1 https://doi.org/https://doi.org/10.1007/...
Resveratrol	AD/TTR+/- mice	Supplementation of 174 mg/kg/day to 5- to 8-month-old	Increased TTR levels and stabilized TTR tetramers, preventing aggregation of Aβ peptides	Santos et al.³⁵35. Santos LM, Rodrigues D, Alemi M, Silva SC, Ribeiro CA, Cardoso I. Resveratrol administration increases transthyretin protein levels, ameliorating AD features: the importance of transthyretin tetrameric stability. Mol Med. 2016 Jun;22(1):597-607. https://doi.org/10.2119/molmed.2016.00124 https://doi.org/https://doi.org/10.2119/...
Resveratrol	CHO-APPswe cell culture	Added in medium (100 μM)	Reduced amyloid burden, expression of APP and its cleavage	Sathya et al.³²32. Sathya M, Moorthi P, Premkumar P, Kandasamy M, Jayachandran KS, Anusuyadevi M. Resveratrol Intervenes Cholesterol- and Isoprenoid-Mediated Amyloidogenic Processing of AβPP in Familial Alzheimer’s Disease. J Alzheimers Dis. 2017 Sep;60(s1):S3-23. https://doi.org/10.3233/JAD-161034 https://doi.org/https://doi.org/10.3233/...

Compound	Sample	Administration	Results	Reference
Resveratrol and sirtinol	SK-N-BE neuroblastoma cells	Added in medium (0, 2.5, 5, 7.5, 10 and 15 µM)	Protected cells from oxidative stress induced by H₂O₂ and 6-OHDA, increasing cell viability. Sirtinol inhibited SIRT1	Albani et al.⁴⁷47. Albani D, Polito L, Batelli S, De Mauro S, Fracasso C, Martelli G, et al. The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by α-synuclein or amyloid-β (1-42) peptide. J Neurochem. 2009 Sep;110(5):1445-56. https://doi.org/10.1111/j.1471-4159.2009.06228.x https://doi.org/https://doi.org/10.1111/...
Resveratrol	Sprague-Dawley rats	Intraperitoneal injection (10, 20 and 40 mg/kg/day)	Improved cognitive impairment and attenuated LPS-induced neuroinflammation in rats by inhibiting the generation of TNF, APP, COX-2 and NF-kB phosphorylation in the hippocampus	Gong et al.⁴¹41. Gong Q, Li F, Jin F, Chan N. Resveratrol Attenuates Neuroinflammation-mediated Cognitive Deficits in Rats. J Health Sci. 2010;56(6):655-63. https://doi.org/https://doi.org/10.1248/jhs.56.655 https://doi.org/https://doi.org/https://...
Resveratrol	Mouse neuroblastoma (N2a) cells	Added in medium (5 µM)	Prevented the abnormal expression of peroxiredoxins and mitochondrial structural genes and preserved mitochondrial function, protecting cells against Aβ toxicity	Manczak et al.⁴²42. Manczak M, Mao P, Calkins MJ, Cornea A, Reddy AP, Murphy MP, et al. Mitochondria-targeted antioxidants protect against amyloid-β toxicity in Alzheimer’s disease neurons. J Alzheimer Dis. 2010 Jun;20(s2):S609-31. https://doi.org/10.3233/JAD-2010-100564 https://doi.org/https://doi.org/10.3233/...
Resveratrol	Sprague-Dawley rats	Injection of 100 μm/5 μL in the lateral ventricle for seven days	Reversed expression of iNOS, reduced amyloid accumulation, prevented neuronal death, increased HO-1 expression, suppressed lipid peroxidation in hippocampus, and improved spatial memory	Huang et al.³⁹39. Huang TC, Lu KT, Wo YYP, Wu YJ, Yang YL. Resveratrol Protects Rats from Aβ-induced Neurotoxicity by the Reduction of iNOS Expression and Lipid Peroxidation. Musaro A, organizador. PLoS One 2011;6(12):e29102. https://doi.org/10.1371/journal.pone.0029102 https://doi.org/https://doi.org/10.1371/...
Resveratrol	BV-2 microglial cells and RAW 264.7 macrophages and APP/PS1 mice	Added in medium and supplementation of 350 mg/kg/day for 15 weeks	Inhibited activation of NF-κB and its target genes (TNF and IL-6) and prevented activation of Aβ-mediated microglia	Capiralla et al.³⁸38. Capiralla H, Vingtdeux V, Zhao H, Sankowski R, Al-Abed Y, Davies P, et al. Resveratrol mitigates lipopolysaccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κB/STAT signaling cascade. J Neurochem. 2012 Feb;120(3):461-72. https://doi.org/10.1111/j.1471-4159.2011.07594.x https://doi.org/https://doi.org/10.1111/...
Resveratrol	PC12 cells	Added in medium (12.5, 25, 50 and 100 μM)	Increased cell viability, reduced apoptosis, attenuated Aβ-induced neurotoxicity and regenerated SIRT1 activity	Feng et al.²2. Feng X, Liang N, Zhu D, Gao Q, Peng L, Dong H, et al. Resveratrol Inhibits β-Amyloid-Induced Neuronal Apoptosis through Regulation of SIRT1-ROCK1 Signaling Pathway. PLoS One. 2013 Mar;8(3):e59888. https://doi.org/10.1371/journal.pone.0059888 https://doi.org/https://doi.org/10.1371/...
Resveratrol and AGK-2	Sprague-Dawley’s astroglia cell culture	Added in medium (2, 10 and 50 μM)	Resveratrol and AGK-2 reduced astrocyte activation and pro-inflammatory mediator production	Scuderi et al.⁴⁹49. Scuderi C, Stecca C, Bronzuoli MR, Rotili D, Valente S, Mai A, et al. Sirtuin modulators control reactive gliosis in an in vitro model of Alzheimer's disease. Front Pharmacol. 2014 May;13(5)89. https://doi.org/10.3389/fphar.2014.00089 https://doi.org/https://doi.org/10.3389/...
Resveratrol and LD55	AβPP/PS1 mice	Supplementation of 100 ppm for 12 months	Resveratrol reduced microglia activation, mainly in the hippocampus. LD55 had the same efficacy, even without the hydroxyl group	Solberg et al.²⁰20. Solberg NO, Chamberlin R, Vigil JR, Deck LM, Heidrich JE, Brown DC, et al. Optical and SPION-enhanced MR imaging shows that trans-stilbene inhibitors of NF-κB concomitantly lower Alzheimer’s Disease plaque formation and microglial activation in AβPP/PS-1 transgenic mouse brain. J Alzheimers Dis. 2014 Mar;40(1):191-212. https://doi.org/10.3233/JAD-131031 https://doi.org/https://doi.org/10.3233/...
Resveratrol	SH-SY5Y neuroblastoma cells	Added in medium (10 and 20 µM)	Reduced ROS production stimulated by AGEs	Ko et al.⁴⁴44. Ko SY, Ko HA, Chu KH, Shieh TM, Chi TC, Chen HI, et al. The possible mechanism of advanced glycation end products (AGEs) for Alzheimer’s disease. PLoS One. 2015 Nov;10(11):e0143345. https://doi.org/10.1371/journal.pone.0143345 https://doi.org/https://doi.org/10.1371/...
Trans-resveratrol	Rat H19-7 neuronal cell line	Added in medium (10 μM)	Attenuated lipid peroxidation, regulated levels of antioxidant enzymes and increased non-enzymatic antioxidants levels	Rege et al.¹⁵15. Rege S, Geetha T, Broderick T, Babu J. Resveratrol protects β amyloid-induced oxidative damage and memory associated proteins in H19-7 hippocampal neuronal cells. Curr Alzheimer Res. 2015;12(2):147-56. https://doi.org/10.2174/1567205012666150204130009 https://doi.org/https://doi.org/10.2174/...
Resveratrol	BV-2 microglial cells	Added in medium (1, 3, 10 or 30 μM)	Reduced ROS production and inhibited NO, TNF and IL-1β production	Yao et al.⁸8. Yao Y, Li J, Niu Y, Yu JQ, Yan L, Miao ZH, et al. Resveratrol inhibits oligomeric Aβ-induced microglial activation via NADPH oxidase. Mol Med Rep. 2015 Aug;12(4):6133-9. https://doi.org/10.3892/mmr.2015.4199 https://doi.org/https://doi.org/10.3892/...
Resveratrol	Wistar female rats	20, 40 and 80 mg/kg/day for 12 weeks	Reduced expression of AGEs and MMP-9, preserving BBB integrity	Zhao et al.⁴⁵45. Zhao HF, Li N, Wang Q, Cheng XJ, Li XM, Liu TT. Resveratrol decreases the insoluble Aβ1-42 level in hippocampus and protects the integrity of the blood-brain barrier in AD rats. Neuroscience. 2015 Dec;310:641-9. https://doi.org/10.1016/j.neuroscience.2015.10.006 https://doi.org/https://doi.org/10.1016/...
Resveratrol	HEK-AbPP cells	Added in medium (0.5 μM)	Ceased most of the neurotoxicity and pro-apoptotic effects on cells treated with γ-secretase inhibitor (LY450139)	Colin et al.⁴⁰40. Colin J, Allouche A, Chauveau F, Corbier C, Pauron-Gregory L, Lanhers M-C, et al. Improved neuroprotection provided by drug combination in neurons exposed to cell-derived soluble amyloid-β peptide. J Alzheimers Dis. 2016 May;52(3):975-87. https://doi.org/10.3233/JAD-151110 https://doi.org/https://doi.org/10.3233/...
Resveratrol	Human neural stem cells (HhNSCs)	Added in medium (10 µM)	Inhibited increase of TNF and IL-1β expression, preventing reduction on cell viability, prevented NF-κB increase, and normalized oxidative stress	Chiang et al.³3. Chiang MC, Nicol CJ, Cheng YC. Resveratrol activation of AMPK-dependent pathways is neuroprotective in human neural stem cells against amyloid-β-induced inflammation and oxidative stress. Neurochem Int. 2018 May;115:1-10. https://doi.org/10.1016/j.neuint.2017.10.002 https://doi.org/https://doi.org/10.1016/...
Resveratrol	Neuro-2a (N2a) cell culture	Added in medium (0, 2.5, 5, 10, 25 and 50 μM)	Decreased cytotoxicity and cellular apoptosis and inhibited tau hyperphosphorylation	He et al.²⁴24. He X, Li Z, Rizak JD, Wu S, Wang Z, He R, et al. Resveratrol attenuates formaldehyde induced hyperphosphorylation of tau protein and cytotoxicity in N2a cells. Front Neurosci. 2017 Jan;31(10):598. https://doi.org/10.3389/fnins.2016.00598 https://doi.org/https://doi.org/10.3389/...
Resveratrol	PC12 cell culture	Added in medium (0, 10, 20 and 40 μM)	Increased cell viability and stimulated HO-1 production	Hui et al.⁴³43. Hui Y, Chengyong T, Cheng L, Haixia H, Yuanda Z, Weihua Y. Resveratrol attenuates the cytotoxicity induced by amyloid-β1-42 in PC12 cells by upregulating heme oxygenase-1 via the PI3K/Akt/Nrf2 pathway. Neurochem Res. 2018 Oct;43(2):297-305. https://doi.org/10.1007/s11064-017-2421-7 https://doi.org/https://doi.org/10.1007/...
Resveratrol	CSF samples of AD humans	Prior treatment with an initial dose of 500 mg/day, increasing every 13 weeks until completion with 1,000 mg twice/day	Attenuated neuroinflammation, reduced proinflammatory markers and MMP-9 in the CSF, attenuated the cognitive and functional decline of individuals	Moussa et al.⁴⁶46. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, et al. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation. 2017 Jan;14(1):1. https://doi.org/10.1186/s12974-016-0779-0 https://doi.org/https://doi.org/10.1186/...
Resveratrol	Rat astrocytes (RA) and microglia N9 cell lines	Added in medium (5, 12.5, and 25 μM in RA cell line and 10, 20, and 40 μM in N9 cell line)	Inhibited the release of inflammatory cytokines by inhibiting NF-κB signaling	Haifeng et al.³⁷37. Haifeng Z, Qian W, Xuejiao C, Xuemin L, Na L. Inhibitive effect of resveratrol on the inflammation in cultured astrocytes and microglia induced by Aβ1-42. Neuroscience 2018 May;379:390-404. https://doi.org/10.1016/j.neuroscience.2018.03.047 https://doi.org/https://doi.org/10.1016/...
Trans-resveratrol, piceatannol and trans-4-hidroxistilbene	Culture of primary neurons in the cortex of Sprague-Dawley rats	Added in medium (20 and 50 μM)	The stilbenoids inhibited Aβ-induced neurotoxicity, resulting in ROS decrease	Wen et al.¹⁷17. Wen H, Fu Z, Wei Y, Zhang X, Ma L, Gu L, et al. Antioxidant Activity and Neuroprotective Activity of Stilbenoids in Rat Primary Cortex Neurons via the PI3K/Akt Signalling Pathway. Molecules. 2018 Sep;23(9):2328. https://doi.org/10.3390/molecules23092328 https://doi.org/https://doi.org/10.3390/...

Compound	Sample	Administration	Results	Reference
Resveratrol	SAMR1 and SAMP8 mice	Supplementation of 1 g/kg/day for seven months	Increased life expectancy, reduced cognitive impairment, amyloid deposition in the hippocampus and tau levels in the cortex and hippocampus, activated AMPK and SIRT1	Porquet et al.⁴⁸48. Porquet D, Casadesús G, Bayod S, Vicente A, Canudas AM, Vilaplana J, et al. Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8. AGE. 2013 Nov;35(5):1851-65. https://doi.org/10.1007/s11357-012-9489-4 https://doi.org/https://doi.org/10.1007/...
Resveratrol	AβPP/PS1 mice	Supplementation of 16 mg/kg/day for 10 months	Prevented short-term memory loss, reduced the amount of amyloid plaques in the hippocampus and cortex, increased levels of mitochondrial complex IV	Porquet et al.⁵¹51. Porquet D, Griñán-Ferré C, Ferrer I, Camins A, Sanfeliu C, del Valle J, et al. Neuroprotective Role of Trans-Resveratrol in a Murine Model of Familial Alzheimer’s Disease. J Alzheimers Dis. 2014;42(4):1209-20. https://doi.org/10.3233/JAD-140444 https://doi.org/https://doi.org/10.3233/...
Resveratrol	Mice	Injection (4 mg/kg)	Reduced the decline in different memory types (working, nonspatial, and locomotor functions) induced by LPS, and increased both NEP and estradiol levels, consequently decreasing Aβ deposition	El-Sayed and Bayan⁵²52. El-Sayed NS, Bayan Y. Possible role of resveratrol targeting estradiol and neprilysin pathways in lipopolysaccharide model of Alzheimer disease. Adv Exp Med Biol. 2015 Oct;822:107-18. https://doi.org/10.1007/978-3-319-08927-0_12 https://doi.org/https://doi.org/10.1007/...
Resveratrol	AβPP/PS1 mice	Oral administration of 20 and 40 mg/kg/day for three weeks	Reduced Aβ-induced impairment on memory and learning, decreased IL-1β, IL-6 and pro-apoptotic protein expression and reversed Aβ42-induced decrease of CREB	Wang et al.¹⁹19. Wang G, Chen L, Pan X, Chen J, Wang L, Wang W, et al. The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling. Oncotarget. 2016 Mar;7(14);17380-92. https://doi.org/10.18632/oncotarget.8041 https://doi.org/https://doi.org/10.18632...
Resveratrol	Sprague-Dawley rats	Injection into the hippocampus (0.5, 1.25, 5, 22, and 44 μM)	Prevented memory and learning impairment and restored the reduction of SIRT1 levels and CREB phosphorylation.	Wang et al.⁵⁰50. Wang R, Zhang Y, Li J, Zhang C. Resveratrol ameliorates spatial learning memory impairment induced by Aβ 1-42 in rats. Neuroscience. 2017 Mar;344:39-47. https://doi.org/10.1016/j.neuroscience.2016.08.051 https://doi.org/https://doi.org/10.1016/...
Resveratrol	3xTg-AD mice	Supplementation of 100 mg/kg/day for 10 months	Improved memory and cognition and reduced anxiety. Increased AMPK, SIRT1 and CREB	Corpas et al.¹⁸18. Corpas R, Griñán-Ferré C, Rodríguez-Farré E, Pallàs M, Sanfeliu C. Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement. Mol Neurobiol. 2018 Jun;56(2):1502-16. https://doi.org/10.1007/s12035-018-1157-y https://doi.org/https://doi.org/10.1007/...

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[1] Correspondence: Júlia Canto e Sousa; Avenida Luís Viana, 3.146/3.100, 41720-200, Pituaçu, Salvador BA, Brazil; E-mail: juliacantonut@gmail.com