Axonal Transport Defects in Alzheimer’s Disease

Molecular Neurobiology - Tập 51 Số 3 - Trang 1309-1321 - 2015
Zi-Xuan Wang1, Lan Tan1, Jin‐Tai Yu1
1Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

Tóm tắt

Từ khóa


Tài liệu tham khảo

Cai Y, Zhang XM, Macklin LN, Cai H, Luo XG, Oddo S, Laferla FM, Struble RG, Rose GM, Patrylo PR, Yan XX (2012) BACE1 elevation is involved in amyloid plaque development in the triple transgenic model of Alzheimer’s disease: differential Abeta antibody labeling of early-onset axon terminal pathology. Neurotox Res 21(2):160–174. doi: 10.1007/s12640-011-9256-9

Ihara M, Polvikoski TM, Hall R, Slade JY, Perry RH, Oakley AE, Englund E, O’Brien JT, Ince PG, Kalaria RN (2010) Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies. Acta Neuropathol 119(5):579–589. doi: 10.1007/s00401-009-0635-8

Hirokawa N, Niwa S, Tanaka Y (2010) Molecular motors in neurons: transport mechanisms and roles in brain function, development, and disease. Neuron 68(4):610–638. doi: 10.1016/j.neuron.2010.09.039

Verhey KJ, Meyer D, Deehan R, Blenis J, Schnapp BJ, Rapoport TA, Margolis B (2001) Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol 152(5):959–970

Jordens I, Fernandez-Borja M, Marsman M, Dusseljee S, Janssen L, Calafat J, Janssen H, Wubbolts R, Neefjes J (2001) The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein–dynactin motors. Curr Biol 11(21):1680–1685

Morfini G, Szebenyi G, Brown H, Pant HC, Pigino G, DeBoer S, Beffert U, Brady ST (2004) A novel CDK5-dependent pathway for regulating GSK3 activity and kinesin-driven motility in neurons. EMBO J 23(11):2235–2245. doi: 10.1038/sj.emboj.7600237

Morfini G, Szebenyi G, Elluru R, Ratner N, Brady ST (2002) Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J 21(3):281–293. doi: 10.1093/emboj/21.3.281

Morfini G, Szebenyi G, Richards B, Brady ST (2001) Regulation of kinesin: implications for neuronal development. Dev Neurosci 23(4–5):364–376

Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjorkblom B, Coffey ET, Bagnato C, Han D, Huang CF, Banker G, Pigino G, Brady ST (2009) Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat Neurosci 12(7):864–871. doi: 10.1038/nn.2346

Morfini G, Pigino G, Szebenyi G, You Y, Pollema S, Brady ST (2006) JNK mediates pathogenic effects of polyglutamine-expanded androgen receptor on fast axonal transport. Nat Neurosci 9(7):907–916. doi: 10.1038/nn1717

Cross DA, Watt PW, Shaw M, van der Kaay J, Downes CP, Holder JC, Cohen P (1997) Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-insensitive pathways in skeletal muscle and adipose tissue. FEBS Lett 406(1–2):211–215

Cook D, Fry MJ, Hughes K, Sumathipala R, Woodgett JR, Dale TC (1996) Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C. EMBO J 15(17):4526–4536

Ratner N, Bloom GS, Brady ST (1998) A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein. J Neurosci Off J Soc Neurosci 18(19):7717–7726

Stagi M, Gorlovoy P, Larionov S, Takahashi K, Neumann H (2006) Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway. FASEB J Off Publ Fed Am Soc Exp Biol 20(14):2573–2575. doi: 10.1096/fj.06-6679fje

Wang J, Yu JT, Tan MS, Jiang T, Tan L (2013) Epigenetic mechanisms in Alzheimer’s disease: Implications for pathogenesis and therapy. Ageing Res Rev 12(4):1024–1041. doi: 10.1016/j.arr.2013.05.003

Muller U, Cristina N, Li ZW, Wolfer DP, Lipp HP, Rulicke T, Brandner S, Aguzzi A, Weissmann C (1994) Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. Cell 79(5):755–765

Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS (2005) Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science 307(5713):1282–1288. doi: 10.1126/science.1105681

Wirths O, Weis J, Szczygielski J, Multhaup G, Bayer TA (2006) Axonopathy in an APP/PS1 transgenic mouse model of Alzheimer’s disease. Acta Neuropathol 111(4):312–319. doi: 10.1007/s00401-006-0041-4

Smith KD, Kallhoff V, Zheng H, Pautler RG (2007) In vivo axonal transport rates decrease in a mouse model of Alzheimer’s disease. NeuroImage 35(4):1401–1408. doi: 10.1016/j.neuroimage.2007.01.046

Kamal A, Stokin GB, Yang Z, Xia CH, Goldstein LS (2000) Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron 28(2):449–459

Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS (2001) Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature 414(6864):643–648. doi: 10.1038/414643a

Muresan Z, Muresan V (2005) Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1. J Cell Biol 171(4):615–625. doi: 10.1083/jcb.200502043

Kuan YH, Gruebl T, Soba P, Eggert S, Nesic I, Back S, Kirsch J, Beyreuther K, Kins S (2006) PAT1a modulates intracellular transport and processing of amyloid precursor protein (APP), APLP1, and APLP2. J Biol Chem 281(52):40114–40123. doi: 10.1074/jbc.M605407200

Araki Y, Kawano T, Taru H, Saito Y, Wada S, Miyamoto K, Kobayashi H, Ishikawa HO, Ohsugi Y, Yamamoto T, Matsuno K, Kinjo M, Suzuki T (2007) The novel cargo Alcadein induces vesicle association of kinesin-1 motor components and activates axonal transport. EMBO J 26(6):1475–1486. doi: 10.1038/sj.emboj.7601609

Vagnoni A, Perkinton MS, Gray EH, Francis PT, Noble W, Miller CC (2012) Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates Abeta production. Hum Mol Genet 21(13):2845–2854. doi: 10.1093/hmg/dds109

Lazarov O, Morfini GA, Lee EB, Farah MH, Szodorai A, DeBoer SR, Koliatsos VE, Kins S, Lee VM, Wong PC, Price DL, Brady ST, Sisodia SS (2005) Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. J Neurosci Off J Soc Neurosci 25(9):2386–2395. doi: 10.1523/JNEUROSCI.3089-04.2005

Vagnoni A, Glennon EB, Perkinton MS, Gray EH, Noble W, Miller CC (2013) Loss of c-Jun N-terminal kinase-interacting protein-1 does not affect axonal transport of the amyloid precursor protein or Abeta production. Hum Mol Genet 22(22):4646–4652. doi: 10.1093/hmg/ddt313

Weaver C, Leidel C, Szpankowski L, Farley NM, Shubeita GT, Goldstein LS (2013) Endogenous GSK-3/shaggy regulates bidirectional axonal transport of the amyloid precursor protein. Traffic 14(3):295–308. doi: 10.1111/tra.12037

Rodrigues EM, Weissmiller AM, Goldstein LS (2012) Enhanced beta-secretase processing alters APP axonal transport and leads to axonal defects. Hum Mol Genet 21(21):4587–4601. doi: 10.1093/hmg/dds297

Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Goldstein LS, Mobley WC (2006) Increased App expression in a mouse model of Down’s syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51(1):29–42. doi: 10.1016/j.neuron.2006.05.022

Satpute-Krishnan P, DeGiorgis JA, Conley MP, Jang M, Bearer EL (2006) A peptide zipcode sufficient for anterograde transport within amyloid precursor protein. Proc Natl Acad Sci U S A 103(44):16532–16537. doi: 10.1073/pnas.0607527103

Henriques AG, Vieira SI, da Cruz ESEF, da Cruz ESOA (2010) Abeta promotes Alzheimer’s disease-like cytoskeleton abnormalities with consequences to APP processing in neurons. J Neurochem 113(3):761–771. doi: 10.1111/j.1471-4159.2010.06643.x

Ding H, Dolan PJ, Johnson GV (2008) Histone deacetylase 6 interacts with the microtubule-associated protein tau. J Neurochem 106(5):2119–2130. doi: 10.1111/j.1471-4159.2008.05564.x

Hiruma H, Katakura T, Takahashi S, Ichikawa T, Kawakami T (2003) Glutamate and amyloid beta-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms. J Neurosci Off J Soc Neurosci 23(26):8967–8977

Rui Y, Li R, Liu Y, Zhu S, Yu X, Sheng Z, Xie Z (2006) Acute effect of beta amyloid on synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks. Cell Biol Int 30(9):733–740. doi: 10.1016/j.cellbi.2006.05.005

Bomfim TR, Forny-Germano L, Sathler LB, Brito-Moreira J, Houzel JC, Decker H, Silverman MA, Kazi H, Melo HM, McClean PL, Holscher C, Arnold SE, Talbot K, Klein WL, Munoz DP, Ferreira ST, De Felice FG (2012) An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease- associated Abeta oligomers. J Clin Invest 122(4):1339–1353. doi: 10.1172/JCI57256

Pigino G, Morfini G, Atagi Y, Deshpande A, Yu C, Jungbauer L, LaDu M, Busciglio J, Brady S (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc Natl Acad Sci U S A 106(14):5907–5912. doi: 10.1073/pnas.0901229106

Decker H, Lo KY, Unger SM, Ferreira ST, Silverman MA (2010) Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons. J Neurosci Off J Soc Neurosci 30(27):9166–9171. doi: 10.1523/JNEUROSCI.1074-10.2010

Zempel H, Thies E, Mandelkow E, Mandelkow EM (2010) Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci Off J Soc Neurosci 30(36):11938–11950. doi: 10.1523/JNEUROSCI.2357-10.2010

Takashima A, Murayama M, Murayama O, Kohno T, Honda T, Yasutake K, Nihonmatsu N, Mercken M, Yamaguchi H, Sugihara S, Wolozin B (1998) Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc Natl Acad Sci U S A 95(16):9637–9641

Tesco G, Tanzi RE (2000) GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin. Effects of the D257/D385A and FAD-linked mutations. Ann N Y Acad Sci 920:227–232

Pigino G, Morfini G, Pelsman A, Mattson MP, Brady ST, Busciglio J (2003) Alzheimer’s presenilin 1 mutations impair kinesin-based axonal transport. J Neurosci Off J Soc Neurosci 23(11):4499–4508

Lazarov O, Morfini GA, Pigino G, Gadadhar A, Chen X, Robinson J, Ho H, Brady ST, Sisodia SS (2007) Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer’s disease-linked mutant presenilin 1. J Neurosci Off J Soc Neurosci 27(26):7011–7020. doi: 10.1523/JNEUROSCI.4272-06.2007

Dolma K, Iacobucci GJ, Hong Zheng K, Shandilya J, Toska E, White JA 2nd, Spina E, Gunawardena S (2014) Presenilin influences glycogen synthase kinase-3 beta (GSK-3beta) for kinesin-1 and dynein function during axonal transport. Hum Mol Genet 23(5):1121–1133. doi: 10.1093/hmg/ddt505

Iqbal K, Grundke-Iqbal I, Zaidi T, Merz PA, Wen GY, Shaikh SS, Wisniewski HM, Alafuzoff I, Winblad B (1986) Defective brain microtubule assembly in Alzheimer’s disease. Lancet 2(8504):421–426

Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83(13):4913–4917

Bramblett GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VM (1993) Abnormal tau phosphorylation at Ser396 in Alzheimer’s disease recapitulates development and contributes to reduced microtubule binding. Neuron 10(6):1089–1099

Dayanandan R, Van Slegtenhorst M, Mack TG, Ko L, Yen SH, Leroy K, Brion JP, Anderton BH, Hutton M, Lovestone S (1999) Mutations in tau reduce its microtubule binding properties in intact cells and affect its phosphorylation. FEBS Lett 446(2–3):228–232

Mudher A, Shepherd D, Newman TA, Mildren P, Jukes JP, Squire A, Mears A, Drummond JA, Berg S, MacKay D, Asuni AA, Bhat R, Lovestone S (2004) GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila. Mol Psychiatry 9(5):522–530. doi: 10.1038/sj.mp.4001483

Ishihara T, Hong M, Zhang B, Nakagawa Y, Lee MK, Trojanowski JQ, Lee VM (1999) Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24(3):751–762

Higuchi M, Zhang B, Forman MS, Yoshiyama Y, Trojanowski JQ, Lee VM (2005) Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathies. J Neurosci Off J Soc Neurosci 25(41):9434–9443. doi: 10.1523/JNEUROSCI.2691-05.2005

Nuydens R, Van Den Kieboom G, Nolten C, Verhulst C, Van Osta P, Spittaels K, Van den Haute C, De Feyter E, Geerts H, Van Leuven F (2002) Coexpression of GSK-3beta corrects phenotypic aberrations of dorsal root ganglion cells, cultured from adult transgenic mice overexpressing human protein tau. Neurobiol Dis 9(1):38–48. doi: 10.1006/nbdi.2001.0454

Bull ND, Guidi A, Goedert M, Martin KR, Spillantini MG (2012) Reduced axonal transport and increased excitotoxic retinal ganglion cell degeneration in mice transgenic for human mutant P301S tau. PLoS One 7(4):e34724. doi: 10.1371/journal.pone.0034724

Zhang B, Higuchi M, Yoshiyama Y, Ishihara T, Forman MS, Martinez D, Joyce S, Trojanowski JQ, Lee VM (2004) Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy. J Neurosci Off J Soc Neurosci 24(19):4657–4667. doi: 10.1523/JNEUROSCI.0797-04.2004

Seitz A, Kojima H, Oiwa K, Mandelkow EM, Song YH, Mandelkow E (2002) Single-molecule investigation of the interference between kinesin, tau and MAP2c. EMBO J 21(18):4896–4905

Kanaan NM, Morfini GA, LaPointe NE, Pigino GF, Patterson KR, Song Y, Andreadis A, Fu Y, Brady ST, Binder LI (2011) Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases. J Neurosci Off J Soc Neurosci 31(27):9858–9868. doi: 10.1523/JNEUROSCI.0560-11.2011

Morfini G, Pigino G, Mizuno N, Kikkawa M, Brady ST (2007) Tau binding to microtubules does not directly affect microtubule-based vesicle motility. J Neurosci Res 85(12):2620–2630. doi: 10.1002/jnr.21154

LaPointe NE, Morfini G, Pigino G, Gaisina IN, Kozikowski AP, Binder LI, Brady ST (2009) The amino terminus of tau inhibits kinesin-dependent axonal transport: implications for filament toxicity. J Neurosci Res 87(2):440–451. doi: 10.1002/jnr.21850

Magnani E, Fan J, Gasparini L, Golding M, Williams M, Schiavo G, Goedert M, Amos LA, Spillantini MG (2007) Interaction of tau protein with the dynactin complex. EMBO J 26(21):4546–4554. doi: 10.1038/sj.emboj.7601878

Ittner LM, Ke YD, Gotz J (2009) Phosphorylated Tau interacts with c-Jun N-terminal kinase-interacting protein 1 (JIP1) in Alzheimer disease. J Biol Chem 284(31):20909–20916. doi: 10.1074/jbc.M109.014472

Gasparini L, Crowther RA, Martin KR, Berg N, Coleman M, Goedert M, Spillantini MG (2011) Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viability. Neurobiol Aging 32(3):419–433. doi: 10.1016/j.neurobiolaging.2009.03.002

Yuan A, Kumar A, Sasaki T, Duff K, Nixon RA (2013) Global axonal transport rates are unaltered in htau mice invivo. J Alzheimer’s Dis 37(3):579–586. doi: 10.3233/JAD-130671

Onishi T, Matsumoto Y, Hattori M, Obayashi Y, Nakamura K, Yano T, Horiguchi T, Iwashita H (2014) Early-onset cognitive deficits and axonal transport dysfunction in P301S mutant tau transgenic mice. Neurosci Res 80:76–85. doi: 10.1016/j.neures.2013.12.006

Tal R, Winter G, Ecker N, Klionsky DJ, Abeliovich H (2007) Aup1p, a yeast mitochondrial protein phosphatase homolog, is required for efficient stationary phase mitophagy and cell survival. J Biol Chem 282(8):5617–5624. doi: 10.1074/jbc.M605940200

Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci Off J Soc Neurosci 29(28):9090–9103. doi: 10.1523/JNEUROSCI.1357-09.2009

Correia SC, Santos RX, Santos MS, Casadesus G, Lamanna JC, Perry G, Smith MA, Moreira PI (2013) Mitochondrial abnormalities in a streptozotocin-induced rat model of sporadic Alzheimer’s disease. Curr Alzheimers Res 10(4):406–419

Scheff SW, DeKosky ST, Price DA (1990) Quantitative assessment of cortical synaptic density in Alzheimer’s disease. Neurobiol Aging 11(1):29–37

Rui Y, Tiwari P, Xie Z, Zheng JQ (2006) Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons. J Neurosci Off J Soc Neurosci 26(41):10480–10487. doi: 10.1523/JNEUROSCI.3231-06.2006

Calkins MJ, Reddy PH (2011) Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer’s disease neurons. Biochim Biophys Acta 1812(4):507–513. doi: 10.1016/j.bbadis.2011.01.007

Zhao XL, Wang WA, Tan JX, Huang JK, Zhang X, Zhang BZ, Wang YH, YangCheng HY, Zhu HL, Sun XJ, Huang FD (2010) Expression of beta-amyloid induced age-dependent presynaptic and axonal changes in Drosophila. J Neurosci Off J Soc Neurosci 30(4):1512–1522. doi: 10.1523/JNEUROSCI.3699-09.2010

Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS (2010) Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A 107(43):18670–18675. doi: 10.1073/pnas.1006586107

Kim C, Choi H, Jung ES, Lee W, Oh S, Jeon NL, Mook-Jung I (2012) HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons. PLoS One 7(8):e42983. doi: 10.1371/journal.pone.0042983

Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK (2006) Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. J Neurosci Off J Soc Neurosci 26(35):9057–9068. doi: 10.1523/JNEUROSCI.1469-06.2006

Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD (2008) Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med 14(10):1097–1105. doi: 10.1038/nm.1868

Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437–1449. doi: 10.1093/hmg/ddl066

Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD (2005) Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J Off Publ Fed Am Soc Exp Biol 19(14):2040–2041. doi: 10.1096/fj.05-3735fje

Aschrafi A, Natera-Naranjo O, Gioio AE, Kaplan BB (2010) Regulation of axonal trafficking of cytochrome c oxidase IV mRNA. Mol Cell Neurosci 43(4):422–430. doi: 10.1016/j.mcn.2010.01.009

Young KJ, Bennett JP (2010) The mitochondrial secret(ase) of Alzheimer’s disease. J Alzheimer’s Dis 20(Suppl 2):S381–S400. doi: 10.3233/JAD-2010-100360

Massaad CA, Amin SK, Hu L, Mei Y, Klann E, Pautler RG (2010) Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer’s disease. PLoS One 5(5):e10561. doi: 10.1371/journal.pone.0010561

Guo L, Du H, Yan S, Wu X, McKhann GM, Chen JX, Yan SS (2013) Cyclophilin D deficiency rescues axonal mitochondrial transport in Alzheimer’s neurons. PLoS One 8(1):e54914. doi: 10.1371/journal.pone.0054914

Yi M, Weaver D, Hajnoczky G (2004) Control of mitochondrial motility and distribution by the calcium signal: a homeostatic circuit. J Cell Biol 167(4):661–672. doi: 10.1083/jcb.200406038

Roh SE, Woo JA, Lakshmana MK, Uhlar C, Ankala V, Boggess T, Liu T, Hong YH, Mook-Jung I, Kim SJ, Kang DE (2013) Mitochondrial dysfunction and calcium deregulation by the RanBP9-cofilin pathway. FASEB J Off Publ Fed Am Soc Exp Biol 27(12):4776–4789. doi: 10.1096/fj.13-234765

Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci Off J Soc Neurosci 30(12):4232–4240. doi: 10.1523/JNEUROSCI.6248-09.2010

Chen Z, Zhong C (2014) Oxidative stress in Alzheimer’s disease. Neurosci Bull 30(2):271–281. doi: 10.1007/s12264-013-1423-y

Eckert A, Nisbet R, Grimm A, Gotz J (2013) March separate, strike together—role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta. doi: 10.1016/j.bbadis.2013.08.013

Nixon RA (2007) Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci 120(Pt 23):4081–4091. doi: 10.1242/jcs.019265

Yu JT, Tan L, Hardy J (2014) Apolipoprotein E in Alzheimer’s disease: an update. Annu Rev Neurosci 37:79–100. doi: 10.1146/annurev-neuro-071013-014300

Yin RH, Yu JT, Tan L (2014) The role of SORL1 in Alzheimer’s disease. Mol Neurobiol. doi: 10.1007/s12035-014-8742-5

Folwell J, Cowan CM, Ubhi KK, Shiabh H, Newman TA, Shepherd D, Mudher A (2010) Abeta exacerbates the neuronal dysfunction caused by human tau expression in a Drosophila model of Alzheimer’s disease. Exp Neurol 223(2):401–409. doi: 10.1016/j.expneurol.2009.09.014

Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L (2010) Tau reduction prevents Abeta-induced defects in axonal transport. Science 330(6001):198. doi: 10.1126/science.1194653

Dawson HN, Cantillana V, Jansen M, Wang H, Vitek MP, Wilcock DM, Lynch JR, Laskowitz DT (2010) Loss of tau elicits axonal degeneration in a mouse model of Alzheimer’s disease. Neuroscience 169(1):516–531. doi: 10.1016/j.neuroscience.2010.04.037

Gunawardena S, Yang G, Goldstein LS (2013) Presenilin controls kinesin-1 and dynein function during APP-vesicle transport invivo. Hum Mol Genet 22(19):3828–3843. doi: 10.1093/hmg/ddt237

Iijima-Ando K, Sekiya M, Maruko-Otake A, Ohtake Y, Suzuki E, Lu B, Iijima KM (2012) Loss of axonal mitochondria promotes tau-mediated neurodegeneration and Alzheimer’s disease-related tau phosphorylation via PAR-1. PLoS Genet 8(8):e1002918. doi: 10.1371/journal.pgen.1002918

Falzone TL, Gunawardena S, McCleary D, Reis GF, Goldstein LS (2010) Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathies. Hum Mol Genet 19(22):4399–4408. doi: 10.1093/hmg/ddq363

Brunden KR, Ballatore C, Lee VM, Smith AB 3rd, Trojanowski JQ (2012) Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies. Biochem Soc Trans 40(4):661–666. doi: 10.1042/BST20120010

Quraishe S, Cowan CM, Mudher A (2013) NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy. Mol Psychiatry 18(7):834–842. doi: 10.1038/mp.2013.32

Bonini SA, Ferrari-Toninelli G, Montinaro M, Memo M (2013) Notch signalling in adult neurons: a potential target for microtubule stabilization. Ther Adv Neurol Disord 6(6):375–385. doi: 10.1177/1756285613490051

Agholme L, Nath S, Domert J, Marcusson J, Kagedal K, Hallbeck M (2014) Proteasome inhibition induces stress kinase dependent transport deficits—implications for Alzheimer’s disease. Mol Cell Neurosci 58:29–39. doi: 10.1016/j.mcn.2013.11.001

Shaw JL, Chang KT (2013) Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3beta signaling. PLoS Genet 9(9):e1003792. doi: 10.1371/journal.pgen.1003792

Sun JH, Yu JT, Tan L (2014) The role of cholesterol metabolism in Alzheimer’s disease. Mol Neurobiol. doi: 10.1007/s12035-014-8749-y