Kalia, L. V. & Lang, A. E. Parkinson's disease. Lancet 386, 896–912 (2015).
Goedert, M., Spillantini, M. G., Del Tredici, K. & Braak, H. 100 years of Lewy pathology. Nature Rev. Neurol. 9, 13–24 (2013).
Hornykiewicz, O. Dopamine (3-hydroxytyramine) in the central nervous system and its relation to the Parkinson syndrome in man [in German]. Dtsch. Med. Wochenschr. 87, 1807–1810 (1962).
Dickson, D. W. Parkinson's disease and parkinsonism: neuropathology. Cold Spring Harb. Perspect. Med 2, a009258 (2012).
Spillantini, M. G. et al. α-Synuclein in Lewy bodies. Nature 388, 839–840 (1997).
Ciechanover, A. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nature Rev. Mol. Cell Biol. 6, 79–87 (2005).
Braak, H. & Braak, E. Pathoanatomy of Parkinson's disease. J. Neurol. 247 (suppl. 2), II3–II10 (2000).
Lin, M. K. & Farrer, M. J. Genetics and genomics of Parkinson's disease. Genome Med. 6, 48 (2014).
Polymeropoulos, M. H. et al. Mapping of a gene for Parkinson's disease to chromosome 4q21-q23. Science 274, 1197–1199 (1996).
Kitada, T. et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608 (1998).
Bonifati, V. et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256–259 (2003).
Valente, E. M. et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304, 1158–1160 (2004).
Zimprich, A. et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601–607 (2004).
Paisán-Ruíz, C. et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595–600 (2004).
Nalls, M. A. et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nature Genet. 46, 989–993 (2014).
International Parkinson Disease Genomics Consortium. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet 377, 641–649 (2011).
Singleton, A. B. et al. α-Synuclein locus triplication causes Parkinson's disease. Science 302, 841 (2003).
Chartier-Harlin, M. C. et al. α-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364, 1167–1169 (2004).
Lee, V. M. & Trojanowski, J. Q. Mechanisms of Parkinson's disease linked to pathological α-synuclein: new targets for drug discovery. Neuron 52, 33–38 (2006).
Farrer, M. et al. α-Synuclein gene haplotypes are associated with Parkinson's disease. Hum. Mol. Genet. 10, 1847–1851 (2001).
Rhinn, H. et al. Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology. Nature Commun. 3, 1084 (2012).
Soldner, F. et al. Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression. Nature 533, 95–99 (2016).
Cooper, A. A. et al. α-Synuclein blocks ER–Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313, 324–328 (2006).
Outeiro, T. F. & Lindquist, S. Yeast cells provide insight into α-synuclein biology and pathobiology. Science 302, 1772–1775 (2003).
Chung, C. Y. et al. Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons. Science 342, 983–987 (2013).
Cortical neurons generated from people with a mutation in α-synuclein exhibit cellular features that could be predicted from the results of an unbiased screen of a yeast α-synuclein toxicity model and that could be reversed using a small-molecule 'hit' from the screen.
Mazzulli, J. R. et al. Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146, 37–52 (2011).
A cellular pathway links Gaucher's disease and PD through impaired lysosomal-enzyme targeting and protein degradation, which suggests that therapeutic targets and strategies might be effective for both disorders.
Mazzulli, J. R., Zunke, F., Isacson, O., Studer, L. & Krainc, D. α-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. Proc. Natl Acad. Sci. USA 113, 1931–1936 (2016).
Long-term cultures of human midbrain dopamine neurons from people with PD or Gaucher's disease exhibit defects in the trafficking of important lysosomal enzymes, which could be rescued by boosting the transport of vesicles.
Volpicelli-Daley, L. A. et al. Formation of α-synuclein Lewy neurite-like aggregates in axons impedes the transport of distinct endosomes. Mol. Biol. Cell 25, 4010–4023 (2014).
Theillet, F. X. et al. Structural disorder of monomeric α-synuclein persists in mammalian cells. Nature 530, 45–50 (2016).
Burré, J., Sharma, M. & Sudhof, T. C. α-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. Proc. Natl Acad. Sci. USA 111, E4274–E4283 (2014).
Bartels, T., Choi, J. G. & Selkoe, D. J. α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477, 107–110 (2011).
Dettmer, U. et al. Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation. Nature Commun. 6, 7314 (2015).
Luk, K. C. et al. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338, 949–953 (2012).
A single, intrastriatal injection of α-synuclein fibrils in wild-type mice initiates the templating and propagation of pathological aggregates, the loss of dopaminergic neurons and motor deficits, providing a direct mechanistic link between the spread of α-synuclein and the pathogenesis of PD.
Volpicelli-Daley, L. A. et al. Exogenous α-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72, 57–71 (2011).
Ryan, S. D. et al. Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2–PGC1α transcription. Cell 155, 1351–1364 (2013).
Pickrell, A. M. et al. Endogenous Parkin preserves dopaminergic substantia nigral neurons following mitochondrial DNA mutagenic stress. Neuron 87, 371–381 (2015).
Youle, R. J. & Narendra, D. P. Mechanisms of mitophagy. Nature Rev. Mol. Cell Biol. 12, 9–14 (2011).
Chen, L., Xie, Z., Turkson, S. & Zhuang, X. A53T human α-synuclein overexpression in transgenic mice induces pervasive mitochondria macroautophagy defects preceding dopamine neuron degeneration. J. Neurosci. 35, 890–905 (2015).
Pickrell, A. M. & Youle, R. J. The roles of PINK1, Parkin, and mitochondrial fidelity in Parkinson's disease. Neuron 85, 257–273 (2015).
Liu, B. et al. The polarisome is required for segregation and retrograde transport of protein aggregates. Cell 140, 257–267 (2010).
Lee, H. J. et al. Autophagic failure promotes the exocytosis and intercellular transfer of α-synuclein. Exp. Mol. Med. 45, e22 (2013).
Kong, S. M. et al. Parkinson's disease-linked human PARK9/ATP13A2 maintains zinc homeostasis and promotes α-synuclein externalization via exosomes. Hum. Mol. Genet. 23, 2816–2833 (2014).
Tsunemi, T., Hamada, K. & Krainc, D. ATP13A2/PARK9 regulates secretion of exosomes and α-synuclein. J. Neurosci. 34, 15281–15287 (2014).
Fellner, L. et al. Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia. Glia 61, 349–360 (2013).
Rannikko, E. H., Weber, S. S. & Kahle, P. J. Exogenous α-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes. BMC Neurosci. 16, 57 (2015).
Kim, C. et al. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nature Commun. 4, 1562 (2013).
Wang, S. et al. α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation. Proc. Natl Acad. Sci. USA 112, E1926–E1935 (2015).
Abeliovich, A. et al. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239–252 (2000).
Chandra, S., Gallardo, G., Fernandez-Chacon, R., Schluter, O. M. & Sudhof, T. C. α-Synuclein cooperates with CSPα in preventing neurodegeneration. Cell 123, 383–396 (2005).
Burré, J. et al. α-Synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329, 1663–1667 (2010).
α-Synuclein is shown to function as a chaperone that facilitates the maintenance of SNARE complexes at the synapse, and Snca Sncb Sncg triple-knockout mice exhibited neurological impairments and deficits in SNARE-complex assembly, revealing an important physiological function for α-synuclein of relevance to neurodegeneration.
Kubo, S. et al. A combinatorial code for the interaction of α-synuclein with membranes. J. Biol. Chem. 280, 31664–31672 (2005).
Nakamura, K. et al. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein α-synuclein. J. Biol. Chem. 286, 20710–20726 (2011).
Gitler, A. D. & Shorter, J. Prime time for α-synuclein. J. Neurosci. 27, 2433–2434 (2007).
West, A. B. et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl Acad. Sci. USA 102, 16842–16847 (2005).
MacLeod, D. et al. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 52, 587–593 (2006).
MacLeod, D. A. et al. RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron 77, 425–439 (2013).
Dodson, M. W., Leung, L. K., Lone, M., Lizzio, M. A. & Guo, M. Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo. Dis. Model. Mech. 7, 1351–1363 (2014).
Martin, I. et al. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell 157, 472–485 (2014).
Waschbüsch, D. et al. LRRK2 transport is regulated by its novel interacting partner Rab32. PLoS ONE 9, e111632 (2014).
Steger, M. et al. Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5, e12813 (2016).
A proteomics approach identifies specific Rab GTPases as physiological targets of the kinase LRRK2; pathogenic variants of LRRK2 increase the phosphorylation of such targets, providing a mechanism that connects mutations in LRRK2 to defects in vesicle-trafficking steps that are orchestrated by Rab GTPases and their effectors.
Beilina, A. et al. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease. Proc. Natl Acad. Sci. USA 111, 2626–2631 (2014).
Tong, Y. et al. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of α-synuclein, and apoptotic cell death in aged mice. Proc. Natl Acad. Sci. USA 107, 9879–9884 (2010).
Fuji, R. N. et al. Effect of selective LRRK2 kinase inhibition on nonhuman primate lung. Sci Transl. Med. 7, 273ra15, (2015).
Herzig, M. C. et al. LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice. Hum. Mol. Genet. 20, 4209–4223 (2011).
Sidransky, E. Gaucher disease and parkinsonism. Mol. Genet. Metab. 84, 302–304 (2005).
Zuckerman, S. et al. Carrier screening for Gaucher disease: lessons for low-penetrance, treatable diseases. J. Am. Med. Assoc. 298, 1281–1290 (2007).
Goker-Alpan, O. et al. Parkinsonism among Gaucher disease carriers. J. Med. Genet. 41, 937–940 (2004).
Schöndorf, D. C. et al. iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis. Nature Commun. 5, 4028 (2014).
Do, C. B. et al. Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease. PLoS Genet. 7, e1002141 (2011).
Rothaug, M. et al. LIMP-2 expression is critical for β-glucocerebrosidase activity and α-synuclein clearance. Proc. Natl Acad. Sci. USA 111, 15573–15578 (2014).
Ramirez, A. et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nature Genet. 38, 1184–1191 (2006).
Gitler, A. D. et al. α-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nature Genet. 41, 308–315 (2009).
Kett, L. R. et al. α-Synuclein-independent histopathological and motor deficits in mice lacking the endolysosomal Parkinsonism protein Atp13a2. J. Neurosci. 35, 5724–5742 (2015).
Usenovic, M., Tresse, E., Mazzulli, J. R., Taylor, J. P. & Krainc, D. Deficiency of ATP13A2 leads to lysosomal dysfunction, α-synuclein accumulation, and neurotoxicity. J. Neurosci. 32, 4240–4246 (2012).
Bento, C. F., Ashkenazi, A., Jimenez-Sanchez, M. & Rubinsztein, D. C. The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway. Nature Commun. 7, 11803 (2016).
Korvatska, O. et al. Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). Hum. Mol. Genet. 22, 3259–3268 (2013).
Dubos, A. et al. Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration. Hum. Mol. Genet. 24, 6736–6755 (2015).
Lesage, S. et al. Loss of VPS13C function in autosomal-recessive Parkinsonism causes mitochondrial dysfunction and increases PINK1/Parkin-dependent mitophagy. Am. J. Hum. Genet. 98, 500–513 (2016).
McMahon, H. T. & Boucrot, E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nature Rev. Mol. Cell Biol. 12, 517–533 (2011).
Zimprich, A. et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am. J. Hum. Genet. 89, 168–175 (2011).
Vilariño-Güell, C. et al. VPS35 mutations in Parkinson disease. Am. J. Hum. Genet. 89, 162–167 (2011).
Parks, W. T. et al. Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-β family of receptor serine-threonine kinases. J. Biol. Chem. 276, 19332–19339 (2001).
Seaman, M. N. & Freeman, C. L. Analysis of the retromer complex–WASH complex interaction illuminates new avenues to explore in Parkinson disease. Commun. Integr. Biol. 7, e29483 (2014).
Zavodszky, E. et al. Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nature Commun. 5, 3828 (2014).
Dhungel, N. et al. Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on α-synuclein. Neuron 85, 76–87 (2015).
Tsika, E. et al. Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration. Hum. Mol. Genet. 23, 4621–4638 (2014).
Arighi, C. N., Hartnell, L. M., Aguilar, R. C., Haft, C. R. & Bonifacino, J. S. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J. Cell Biol. 165, 123–133 (2004).
Hierro, A. et al. Functional architecture of the retromer cargo-recognition complex. Nature 449, 1063–1067 (2007).
McGough, I. J. et al. Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation. Curr. Biol. 24, 1670–1676 (2014).
Miura, E. et al. VPS35 dysfunction impairs lysosomal degradation of α-synuclein and exacerbates neurotoxicity in a Drosophila model of Parkinson's disease. Neurobiol. Dis. 71, 1–13 (2014).
Tang, F. L. et al. VPS35 in dopamine neurons is required for endosome-to-Golgi retrieval of Lamp2a, a receptor of chaperone-mediated autophagy that is critical for α-synuclein degradation and prevention of pathogenesis of Parkinson's disease. J. Neurosci. 35, 10613–10628 (2015).
Vilariño-Güell, C. et al. DNAJC13 mutations in Parkinson disease. Hum. Mol. Genet. 23, 1794–1801 (2014).
Edvardson, S. et al. A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism. PLoS ONE 7, e36458 (2012).
Quadri, M. et al. Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism. Hum. Mutat. 34, 1208–1215 (2013).
Krebs, C. E. et al. The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures. Hum. Mutat. 34, 1200–1207 (2013).
Wilson, G. R. et al. Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology. Am. J. Hum. Genet. 95, 729–735 (2014).
Nemani, V. M. et al. Increased expression of α-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65, 66–79 (2010).
Arranz, A. M. et al. LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J. Cell Sci. 128, 541–552 (2015).
Munsie, L. N. et al. Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson's disease VPS35 mutation p.D620N. Hum. Mol. Genet. 24, 1691–1703 (2015).
Deng, H. X. et al. Identification of TMEM230 mutations in familial Parkinson's disease. Nature Genet. 48, 733–739 (2016).
Satake, W. et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nature Genet. 41, 1303–1307 (2009).
Simón-Sánchez, J. et al. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nature Genet. 41, 1308–1312 (2009).
Ishizawa, T., Mattila, P., Davies, P., Wang, D. & Dickson, D. W. Colocalization of tau and α-synuclein epitopes in Lewy bodies. J. Neuropathol. Exp. Neurol. 62, 389–397 (2003).
Cushman, M., Johnson, B. S., King, O. D., Gitler, A. D. & Shorter, J. Prion-like disorders: blurring the divide between transmissibility and infectivity. J. Cell Sci. 123, 1191–1201 (2010).
Jucker, M. & Walker, L. C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501, 45–51 (2013).
Clavaguera, F. et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc. Natl Acad. Sci. USA 110, 9535–9540 (2013).
Bae, E. J. et al. Glucocerebrosidase depletion enhances cell-to-cell transmission of α-synuclein. Nature Commun. 5, 4755 (2014).
Walsh, D. M. & Selkoe, D. J. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nature Rev. Neurosci. 17, 251–260 (2016).
Kannarkat, G. T., Boss, J. M. & Tansey, M. G. The role of innate and adaptive immunity in Parkinson's disease. J. Parkinsons Dis. 3, 493–514 (2013).
Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).
Czirr, E. & Wyss-Coray, T. The immunology of neurodegeneration. J. Clin. Invest. 122, 1156–1163 (2012).
Harms, A. S. et al. MHCII is required for α-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration. J. Neurosci. 33, 9592–9600 (2013).
Su, X. et al. Synuclein activates microglia in a model of Parkinson's disease. Neurobiol. Aging 29, 1690–1701 (2008).
Kim, C. et al. Antagonizing neuronal Toll-like receptor 2 prevents synucleinopathy by activating autophagy. Cell Rep. 13, 771–782 (2015).
Lee, H. J., Suk, J. E., Bae, E. J. & Lee, S. J. Clearance and deposition of extracellular α-synuclein aggregates in microglia. Biochem. Biophys. Res. Commun. 372, 423–428 (2008).
Zhang, W. et al. Aggregated α-synuclein activates microglia: a process leading to disease progression in Parkinson's disease. FASEB J. 19, 533–542 (2005).
Conway, K. A., Rochet, J. C., Bieganski, R. M. & Lansbury, P. T. Jr. Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct. Science 294, 1346–1349 (2001).
Martinez-Vicente, M. et al. Dopamine-modified α-synuclein blocks chaperone-mediated autophagy. J. Clin. Invest. 118, 777–788 (2008).
Mosharov, E. V. et al. Interplay between cytosolic dopamine, calcium, and α-synuclein causes selective death of substantia nigra neurons. Neuron 62, 218–229 (2009).
Maday, S., Wallace, K. E. & Holzbaur, E. L. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J. Cell Biol. 196, 407–417 (2012).
Ashrafi, G., Schlehe, J. S., LaVoie, M. J. & Schwarz, T. L. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J. Cell Biol. 206, 655–670 (2014).
Chan, C. S. et al. 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 447, 1081–1086 (2007).
Nixon, R. A. The role of autophagy in neurodegenerative disease. Nature Med. 19, 983–997 (2013).
Small, S. A. & Petsko, G. A. Retromer in Alzheimer disease, Parkinson disease and other neurological disorders. Nature Rev. Neurosci. 16, 126–132 (2015).
Schneider, J. L. & Cuervo, A. M. Autophagy and human disease: emerging themes. Curr. Opin. Genet. Dev. 26, 16–23 (2014).
Wong, Y. C. & Holzbaur, E. L. Autophagosome dynamics in neurodegeneration at a glance. J. Cell Sci. 128, 1259–1267 (2015).
Decressac, M. et al. TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity. Proc. Natl Acad. Sci. USA 110, E1817–E1826 (2013).
Richter, F. et al. A GCase chaperone improves motor function in a mouse model of synucleinopathy. Neurotherapeutics 11, 840–856 (2014).
Daher, J. P. et al. Leucine-rich repeat kinase 2 (LRRK2) pharmacological inhibition abates α-synuclein gene-induced neurodegeneration. J. Biol. Chem. 290, 19433–19444 (2015).
Mecozzi, V. J. et al. Pharmacological chaperones stabilize retromer to limit APP processing. Nature Chem. Biol. 10, 443–449 (2014).
The identification of a small molecule that increases the stability of the retromer complex and enhances its function, suggesting that such small molecules might also be effective at boosting retromer function in models of PD.
Tran, H. T. et al. α-Synuclein immunotherapy blocks uptake and templated propagation of misfolded α-synuclein and neurodegeneration. Cell Rep. 7, 2054–2065 (2014).
Lazarou, M. et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524, 309–314 (2015).
Two receptors, optineurin and CALCOCO2 (also known as NDP52), were identified as important targets of PINK1 for recruitment to damaged mitochondria and for the initiation of selective autophagy (mitophagy).
Südhof, T. C. The molecular machinery of neurotransmitter release (Nobel lecture). Angew. Chem. Int. Edn Engl. 53, 12696–12717 (2014).
Sanders, D. W., Kaufman, S. K., Holmes, B. B. & Diamond, M. I. Prions and protein assemblies that convey biological information in health and disease. Neuron 89, 433–448 (2016).
Stenmark, H. Rab GTPases as coordinators of vesicle traffic. Nature Rev. Mol. Cell Biol. 10, 513–525 (2009).
Luzio, J. P., Hackmann, Y., Dieckmann, N. M. & Griffiths, G. M. The biogenesis of lysosomes and lysosome-related organelles. Cold Spring Harb. Perspect. Biol. 6, a016840 (2014).
Lynch-Day, M. A., Mao, K., Wang, K., Zhao, M. & Klionsky, D. J. The role of autophagy in Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a009357 (2012).
Wong, Y. C. & Holzbaur, E. L. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc. Natl Acad. Sci. USA 111, E4439–E4448 (2014).