Progress in Caenorhabditis elegans as a Degenerative Disease Model for Molecular Pathways Studying

doi:10.12300/j.issn.1674-5817.2025.134

Abstract

Abstract:

With the acceleration of population aging in China, the number of patients with degenerative diseases has exceeded ten million, urgently requiring efficient mechanism research and drug screening systems. Caenorhabditis elegans, due to its short life cycle, low cost, and convenient genetic manipulation, has become an important model organism for investigating neurodegenerative diseases. Through heterologous expression of amyloid β-protein (Aβ), α-synuclein (α-Syn), mutant superoxide dismutase 1 (SOD1), etc., or constructing mutants using CRISPR/Cas9 gene editing (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9, CRISPR/Cas9), typical pathological features of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) can be reproduced in Caenorhabditis elegans. By integrating RNA interference (RNAi) and compound screening, the Caenorhabditis elegans model has revealed core pathological pathways such as proteostasis, autophagy, and mitochondrial function, and identified multiple potential targets. In the future, relying on the unique strengths of Caenorhabditis elegans in genetic operability, phenotypic quantification, and screening scale, combined with cross-species validation using multiple models, a more predictive and translatable degenerative disease research and intervention system is expected to be established.

Key words: Caenorhabditis elegans, Degenerative diseases, Model organism, Neurodegenerative diseases

CLC Number:

R-332

SUN Han,GUO Peng,YU Xinhe,et al. Progress in Caenorhabditis elegans as a Degenerative Disease Model for Molecular Pathways Studying[J]. Laboratory Animal and Comparative Medicine, 2025, 45(6): 738-751. DOI: 10.12300/j.issn.1674-5817.2025.134.

Figures/Tables 4

References 79

[1]	HOU Y, DAN X, BABBAR M, WEI Y, HASSELBALCH S G, CROTEAU D L, BOHR V A.　Ageing as a risk factor for neurodegenerative disease[J]. Nat Rev Neurol, 2019, 15(10): 565–581. DOI: 10.1038/s41582-019-0244-7 .
[2]	THE C. ELEGANS SEQUENCING CONSORTIUM. Genome sequence of the nematode C. elegans: a platform for investigating biology[J]. Science, 1998, 282(5396): 2012-2018. DOI: 10.1126/science.282.5396.2012 .
[3]	CULETTO E, SATTELLE D B. A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes[J]. Hum Mol Genet, 2000, 9(6): 869-877. DOI: 10.1093/hmg/9.6.869 .
[4]	SHAYE D D, GREENWALD I. OrthoList: a compendium of C. elegans genes with human orthologs[J]. PLoS One, 2011, 6(5): 1-12. DOI: 10.1371/journal.pone.0020085 .
[5]	BARGMANN C I, HORVITZ H R. Control of larval development by chemosensory neurons in Caenorhabditis elegans [J]. Science, 1991, 251(4998): 1243-1246. DOI: 10.1126/science. 2006412 .
[6]	GRAY J M, KAROW D S, LU H, et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue[J]. Nature, 2004, 430(6997): 317-322. DOI: 10.1038/nature02714 .
[7]	GILES A C, ROSE J K, RANKIN C H. Investigations of learning and memory in Caenorhabditis elegans [J]. Int Rev Neurobiol, 2006, 69: 37-71. DOI: 10.1016/S0074-7742(05)69002-2 .
[8]	HERMS J, ANLIKER B, HEBER S, et al. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members[J]. EMBO J, 2004, 23(20): 4106-4115. DOI: 10.1038/sj.emboj.7600390 .
[9]	DUAN D S, GOEMANS N, TAKEDA S, et al. Duchenne muscular dystrophy[J]. Nat Rev Dis Primers, 2021, 7: 13. DOI: 10.1038/s41572-021-00248-3 .
[10]	HAENGGI T, FRITSCHY J M. Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue[J]. Cell Mol Life Sci, 2006, 63(14): 1614-1631. DOI: 10.1007/s00018-005-5461-0 .
[11]	BRENNER S. The genetics of Caenorhabditis elegans [J]. Genetics, 1974, 77(1): 71-94. DOI: 10.1093/genetics/77.1.71 .
[12]	GIUGIA J, GIESELER K, ARPAGAUS M, et al. Mutations in the dystrophin-like dys-1 gene of Caenorhabditis elegans result in reduced acetylcholinesterase activity[J]. FEBS Lett, 1999, 463(3): 270-272. DOI: 10.1016/s0014-5793(99)01651-8 .
[13]	KRAJACIC P, HERMANOWSKI J, LOZYNSKA O, et al. C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes[J]. Physiol Genomics, 2009, 40(1): 8-14. DOI: 10.1152/physiolgenomics.00106.2009 .
[14]	ARRIBERE J A, FIRE A Z. Nonsense mRNA suppression via nonstop decay[J]. eLife, 2018, 7: 1-23. DOI: 10.7554/eLife.33292 .
[15]	GLOVER M L, BURROUGHS A M, MONEM P C, et al. NONU-1 encodes a conserved endonuclease required for mRNA translation surveillance[J]. Cell Rep, 2020, 30(13): 4321-4331.e4. DOI: 10.1016/j.celrep.2020.03.023 .
[16]	PALIKARAS K, LIONAKI E, TAVERNARAKIS N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans [J]. Nature, 2015, 521(7553): 525-528. DOI: 10.1038/nature14300 .
[17]	HUYNH J M, DANG H, FARES H. Measurement of lysosomal size and lysosomal marker intensities in adult Caenorhabditis elegans [J]. Bio Protoc, 2018, 8(3): 1-12. DOI: 10.21769/BioProtoc.2724 .
[18]	KUKHTAR D, RUBIO-PEÑA K, SERRAT X, et al. Mimicking of splicing-related retinitis pigmentosa mutations in C. elegans allow drug screens and identification of disease modifiers[J]. Hum Mol Genet, 2020, 29(5): 756-765. DOI: 10.1093/hmg/ddz315 .
[19]	LINK C D. Expression of human beta-amyloid peptide in transgenic Caenorhabditis elegans [J]. Proc Natl Acad Sci USA, 1995, 92(20): 9368-9372. DOI: 10.1073/pnas.92.20.9368 .
[20]	KRAEMER B C, ZHANG B, LEVERENZ J B, et al. Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy[J]. Proc Natl Acad Sci USA, 2003, 100(17): 9980-9985. DOI: 10.1073/pnas.1533448100 .
[21]	LAKSO M, VARTIAINEN S, MOILANEN A M, et al. Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein[J]. J Neurochem, 2003, 86(1): 165-172. DOI: 10.1046/j.1471-4159.2003.01809.x .
[22]	FABER P W, ALTER J R, MACDONALD M E, et al. Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron[J]. Proc Natl Acad Sci USA, 1999, 96(1): 179-184. DOI: 10.1073/pnas.96.1.179 .
[23]	LI J, HUANG K X, LE W D. Establishing a novel C. elegans model to investigate the role of autophagy in amyotrophic lateral sclerosis[J]. Acta Pharmacol Sin, 2013, 34(5): 644-650. DOI: 10.1038/aps.2012.190 .
[24]	RING S, WEYER S W, KILIAN S B, et al. The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice[J]. J Neurosci, 2007, 27(29): 7817-7826. DOI: 10.1523/JNEUROSCI.1026-07.2007 .
[25]	WASCO W, BUPP K, MAGENDANTZ M, et al. Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor[J]. Proc Natl Acad Sci USA, 1992, 89(22): 10758-10762. DOI: 10.1073/pnas.89.22.10758 .
[26]	DAIGLE I, LI C. Apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor[J]. Proc Natl Acad Sci USA, 1993, 90(24): 12045-12049. DOI: 10.1073/pnas.90.24.12045 .
[27]	LEE V M, OTVOS L Jr, CARDEN M J, et al. Identification of the major multiphosphorylation site in mammalian neurofilaments[J]. Proc Natl Acad Sci USA, 1988, 85(6): 1998-2002. DOI: 10.1073/pnas.85.6.1998 .
[28]	MCCOLL G, ROBERTS B R, GUNN A P, et al. The Caenorhabditis elegans Aβ_1-42 model of Alzheimer disease predominantly expresses Aβ_3-42 [J]. J Biol Chem, 2009, 284(34): 22697-22702. DOI: 10.1074/jbc.C109.028514 .
[29]	MANGO S E. Stop making nonSense: the C. elegans smg genes[J]. Trends Genet, 2001, 17(11): 646-653. DOI: 10.1016/s0168-9525(01)02479-9 .
[30]	LINK C D, TAFT A, KAPULKIN V, et al. Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model[J]. Neurobiol Aging, 2003, 24(3): 397-413. DOI: 10.1016/s0197-4580(02)00224-5 .
[31]	LU T, ARON L, ZULLO J, et al. REST and stress resistance in ageing and Alzheimer's disease[J]. Nature, 2014, 507(7493): 448-454. DOI: 10.1038/nature13163 .
[32]	SIDDIQUI A A, MERQUIOL E, BRUCK-HAIMSON R, et al. Cathepsin B promotes Aβ proteotoxicity by modulating aging regulating mechanisms[J]. Nat Commun, 2024, 15(1): 8564. DOI: 10.1038/s41467-024-52540-x .
[33]	MARIANI E, POLIDORI M C, CHERUBINI A, et al. Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2005, 827(1): 65-75. DOI: 10.1016/j.jchromb. 2005.04.023 .
[34]	KRAEMER B C, BURGESS J K, CHEN J H, et al. Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans [J]. Hum Mol Genet, 2006, 15(9): 1483-1496. DOI: 10.1093/hmg/ddl067 .
[35]	Diomede L., et al. Expression of A2V-mutated Aβ in Caenorhabditis elegans results in oligomer formation and toxicity[J]. Neurobiol Dis, 2014. 62(100): p. 521-32.
[36]	Huang A, Stultz CM. The effect of a DeltaK280 mutation on the unfolded state of a microtubule-binding repeat in Tau[J]. PLoS Comput Biol. 2008 Aug 22;4(8):e1000155.
[37]	Tiwari V, Buvarp E, Borbolis F, et al. Loss of DNA glycosylases improves health and cognitive function in a C. elegans model of human tauopathy[J]. Nucleic Acids Res. 2024 Oct 14;52(18):10965-10985.
[38]	FANG E F, HOU Y J, PALIKARAS K, et al. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer's disease[J]. Nat Neurosci, 2019, 22(3): 401-412. DOI: 10.1038/s41593-018-0332-9 .
[39]	MACDONALD M. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes[J]. Cell, 1993, 72(6): 971-983. DOI: 10.1016/0092-8674(93)90585-e .
[40]	COSTA M D, MACIEL P. Modifier pathways in polyglutamine (PolyQ) diseases: from genetic screens to drug targets[J]. Cell Mol Life Sci, 2022, 79(5): 1-31. DOI: 10.1007/s00018-022-04280-8 .
[41]	ADAMLA F, IGNATOVA Z. Somatic expression of unc-54 and vha-6 mRNAs declines but not pan-neuronal rgef-1 and unc-119 expression in aging Caenorhabditis elegans [J]. Sci Rep, 2015, 5: 1-10. DOI: 10.1038/srep10692 .
[42]	MARCH Z M, MACK K L, SHORTER J. AAA+ protein-based technologies to counter neurodegenerative disease[J]. Biophys J, 2019, 116(8): 1380-1385. DOI: 10.1016/j.bpj. 2019. 03.007 .
[43]	MOUCHIROUD L, HOUTKOOPER R H, MOULLAN N, et al. The NAD⁺/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling[J]. Cell, 2013, 154(2): 430-441. DOI: 10.1016/j.cell.2013.06.016 .
[44]	SHIN B H, LIM Y, OH H J, et al. Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy[J]. PLoS One, 2013, 8(6): 1-10. DOI: 10.1371/journal.pone.0064953 .
[45]	GAETA A L, CALDWELL K A, CALDWELL G A. Found in translation: the utility of C. elegans alpha-synuclein models of Parkinson's disease[J]. Brain Sci, 2019, 9(4): 1-15. DOI: 10.3390/brainsci9040073 .
[46]	BLIEDERHAEUSER C, GROZDANOV V, SPEIDEL A, et al. Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes[J]. Acta Neuropathol, 2016, 131(3): 379-391. DOI: 10.1007/s00401-015-1504-2 .
[47]	BELLOMO G, PACIOTTI S, GATTICCHI L, et al. The vicious cycle between α-synuclein aggregation and autophagic-lysosomal dysfunction[J]. Mov Disord, 2020, 35(1): 34-44. DOI: 10.1002/mds.27895 .
[48]	MAO X B, OU M T, KARUPPAGOUNDER S S, et al. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3[J]. Science, 2016, 353(6307): 1-33. DOI: 10.1126/science.aah3374 .
[49]	PRICE A, MANZONI C, COOKSON M R, et al. The LRRK2 signalling system[J]. Cell Tissue Res, 2018, 373(1): 39-50. DOI: 10.1007/s00441-017-2759-9 .
[50]	TULLET J M A, ARAIZ C, SANDERS M J, et al. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans [J]. PLoS Genet, 2014, 10(2): 1-16. DOI: 10.1371/journal.pgen.1004109 .
[51]	DHONDT I, PETYUK V A, CAI H H, et al. FOXO/DAF-16 activation slows down turnover of the majority of proteins in C. elegans [J]. Cell Rep, 2016, 16(11): 3028-3040. DOI: 10.1016/j.celrep.2016.07.088 .
[52]	SALAŠOVÁ A, YOKOTA C, POTĚŠIL D, et al. A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway[J]. Mol Neurodegener, 2017, 12(1): 1-19. DOI: 10.1186/s13024-017-0193-9 .
[53]	ARBO B D, ANDRÉ-MIRAL C, NASRE-NASSER R G, et al. Resveratrol derivatives as potential treatments for Alzheimer's and Parkinson's disease[J]. Front Aging Neurosci, 2020, 12: 1-15. DOI: 10.3389/fnagi.2020.00103 .
[54]	CHEN L L, ZHANG S M, LIU S, et al. Amyotrophic lateral sclerosis mechanism: insights from the Caenorhabditis elegans models[J]. Cells, 2024, 13(1): 1-18. DOI: 10.3390/cells13010099 .
[55]	WANG J O, FARR G W, HALL D H, et al. An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans [J]. PLoS Genet, 2009, 5(1): 1-14. DOI: 10.1371/journal.pgen.1000350 .
[56]	ZHONG Y W, WANG J O, HENDERSON M J, et al. Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus[J]. eLife, 2017, 6: 1-23. DOI: 10.7554/eLife.23759 .
[57]	OGAWA M, SHIDARA H, OKA K, et al. Cysteine residues in Cu, Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis[J]. Biochem Biophys Res Commun, 2015, 463(4): 1196-1202. DOI: 10.1016/j.bbrc.2015.06.084 .
[58]	SILVA M C, FOX S, BEAM M, et al. A genetic screening strategy identifies novel regulators of the proteostasis network[J]. PLoS Genet, 2011, 7(12): 1-15. DOI: 10.1371/journal.pgen.1002438 .
[59]	ZHANG T, PERIZ G, LU Y N, et al. USP7 regulates ALS-associated proteotoxicity and quality control through the NEDD4L-SMAD pathway[J]. Proc Natl Acad Sci USA, 2020, 117(45): 28114-28125. DOI: 10.1073/pnas.2014349117 .
[60]	XU H, JIA C C, CHENG C, et al. Activation of autophagy attenuates motor deficits and extends lifespan in a C. elegans model of ALS[J]. Free Radic Biol Med, 2022, 181: 52-61. DOI: 10.1016/j.freeradbiomed.2022.01.030 .
[61]	ZHANG T, MULLANE P C, PERIZ G, et al. TDP-43 neurotoxicity and protein aggregation modulated by heat shock factor and insulin/IGF-1 signaling[J]. Hum Mol Genet, 2011, 20(10): 1952-1965. DOI: 10.1093/hmg/ddr076 .
[62]	ASH P E A, ZHANG Y J, ROBERTS C M, et al. Neurotoxic effects of TDP-43 overexpression in C. elegans [J]. Hum Mol Genet, 2010, 19(16): 3206-3218. DOI: 10.1093/hmg/ddq230 .
[63]	VACCARO A, TAUFFENBERGER A, AGGAD D, et al. Mutant TDP-43 and FUS cause age-dependent paralysis and neurodegeneration in C. elegans [J]. PLoS One, 2012, 7(2): 1-10. DOI: 10.1371/journal.pone.0031321 .
[64]	LIACHKO N F, GUTHRIE C R, KRAEMER B C. Phosphorylation promotes neurotoxicity in a Caenorhabditis elegans model of TDP-43 proteinopathy[J]. J Neurosci, 2010, 30(48): 16208-16219. DOI: 10.1523/JNEUROSCI.2911-10.2010 .
[65]	LIACHKO N F, MCMILLAN P J, GUTHRIE C R, et al. CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration[J]. Ann Neurol, 2013, 74(1): 39-52. DOI: 10.1002/ana.23870 .
[66]	AARON C, BEAUDRY G, PARKER J A, et al. Maple syrup decreases TDP-43 proteotoxicity in a Caenorhabditis elegans model of amyotrophic lateral sclerosis (ALS)[J]. J Agric Food Chem, 2016, 64(17): 3338-3344. DOI: 10.1021/acs.jafc.5b05432 .
[67]	MURAKAMI T, YANG S P, XIE L, et al. ALS mutations in FUS cause neuronal dysfunction and death in Caenorhabditis elegans by a dominant gain-of-function mechanism[J]. Hum Mol Genet, 2012, 21(1): 1-9. DOI: 10.1093/hmg/ddr417 .
[68]	VÉRIÈPE J, FOSSOUO L, PARKER J A. Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons[J]. Nat Commun, 2015, 6: 1-9. DOI: 10.1038/ncomms8319 .
[69]	TOSSING G, LIVERNOCHE R, MAIOS C, et al. Genetic and pharmacological PARP inhibition reduces axonal degeneration in C. elegans models of ALS[J]. Hum Mol Genet, 2022, 31(19): 3313-3324. DOI: 10.1093/hmg/ddac116 .
[70]	LABARRE A, GUITARD E, TOSSING G, et al. Fatty acids derived from the probiotic Lacticaseibacillus rhamnosus HA-114 suppress age-dependent neurodegeneration[J]. Commun Biol, 2022, 5(1): 1-19. DOI: 10.1038/s42003-022-04295-8 .
[71]	WANG X, HAO L M, SAUR T, et al. Forward genetic screen in Caenorhabditis elegans suggests F57A10.2 and acp-4 as suppressors of C9ORF72 related phenotypes[J]. Front Mol Neurosci, 2016, 9: 1-10. DOI: 10.3389/fnmol.2016.00113 .
[72]	SNOZNIK C, MEDVEDEVA V, MOJSILOVIC-PETROVIC J, et al. The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of C9orf72 dipeptide toxicity[J]. Proc Natl Acad Sci USA, 2021, 118(40): 1-10. DOI: 10.1073/pnas.2104664118 .
[73]	PULEO N, LAMITINA T. The conserved multi-functional nuclear protein dss-1/Sem1 is required for C9orf72-associated ALS/FTD dipeptide toxicity[J]. MicroPubl Biol, 2020: 1-5. DOI: 10.17912/micropub.biology.000262 .
[74]	CHANG M Y, CAI Y, GAO Z H, et al. Duchenne muscular dystrophy: pathogenesis and promising therapies[J]. J Neurol, 2023, 270(8): 3733-3749. DOI: 10.1007/s00415-023-11796-x .
[75]	WU X T, NAGASAWA S, MUTO K, et al. Mitochonic acid 5 improves Duchenne muscular dystrophy and Parkinson's disease model of Caenorhabditis elegans [J]. Int J Mol Sci, 2022, 23(17): 1-15. DOI: 10.3390/ijms23179572 .
[76]	YOSHINA S, IZUHARA L, MASHIMA R, et al. Febuxostat ameliorates muscle degeneration and movement disorder of the dystrophin mutant model in Caenorhabditis elegans [J]. J Physiol Sci, 2023, 73(1): 1-9. DOI: 10.1186/s12576-023-00888-y .
[77]	CARRE-PIERRAT M, MARIOL M C, CHAMBONNIER L, et al. Blocking of striated muscle degeneration by serotonin in C. elegans [J]. J Muscle Res Cell Motil, 2006, 27(3-4): 253-258. DOI: 10.1007/s10974-006-9070-9 .
[78]	NYAMSUREN O, FAGGIONATO D, LOCH W, et al. A mutation in CHN-1/CHIP suppresses muscle degeneration in Caenorhabditis elegans [J]. Dev Biol, 2007, 312(1): 193-202. DOI: 10.1016/j.ydbio.2007.09.033 .
[79]	ELLWOOD R A, SLADE L, LEWIS J, et al. Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy[J]. Commun Biol, 2022, 5: 1-12. DOI: 10.1038/s42003-022-04212-z .

疾病 Diseases	定义/特征 Definition/Characteristics	秀丽隐杆线虫模型 Caenorhabditis elegans models
杜氏肌营养不良症 Duchenne muscular dystrophy (DMD)	X染色体连锁隐性遗传，肌肉纤维逐渐坏死和假性肥大	dys-1; ace-1^[12]
肢带型肌营养不良 Limb-girdle muscular dystrophy (LGMD)	累及肩胛带与骨盆带，表现为对称性近端肌无力	LS587; giv otIs117^[13]
肌少症 Sarcopenia	衰老引起的骨骼肌质量显著减少，力量减弱	PD2856; PD2859; PD4092^[14];WJA780^[15]
线粒体肌病 Mitochondrial myopathies	线粒体功能障碍引起的骨骼肌病变	dct-1; allo-1^[16]
糖原累积病 Glycogen storage diseases	酶缺陷导致糖原异常积聚，常见于婴幼儿	RT258;VK2882; pwIs50^[17]
视网膜色素变性 Retinitis pigmentosa (RP)	感光细胞退化，以夜盲和视野缩小为早期表现	snrp-200; prp-8^[18]
骨质疏松症 Osteoporosis	骨密度下降，骨小梁破坏，易致脆性骨折	无
马凡综合征 Marfan syndrome	FBN1基因突变致结缔组织发育异常，累及骨、心血管、眼等系统	无
家族黑蒙性痴呆症 Tay-Sachs disease	HEXA基因突变，溶酶体中GM2神经节苷脂异常积聚	无
脊髓小脑性共济失调 Spinocerebellar ataxia	以共济失调为主要表现的常染色体显性遗传病	无
尼曼-皮克病 Niemann-Pick disease	脂类代谢障碍致肝脾大和神经系统损害	无
阿尔茨海默病 Alzheimer's disease (AD)	β淀粉样蛋白沉积和tau蛋白异常磷酸化引起的认知功能持续退化	Aβ₁_-₄₂^[19]
帕金森病 Parkinson's disease (PD)	黑质多巴胺能神经元丢失，表现为震颤、运动迟缓等	P301L；V337M^[20]；A53T^[21]
亨廷顿病 Huntington's disease (HD)	HTT基因CAG重复扩增引起基底节神经元退化，表现为舞蹈样运动和精神症状	HTN-Q150^[22]
肌萎缩侧索硬化 Amyotrophic lateral sclerosis (ALS)	上下运动神经元退化，导致肌肉萎缩、瘫痪	G93A SOD1^[23]
进行性核上性麻痹 Progressive supranuclear palsy	以垂直眼动障碍、姿势不稳和额叶认知障碍为特征的tau蛋白病	无
多发性硬化症 Multiple sclerosis	中枢神经系统白质脱髓鞘，伴随神经功能缺失	无

疾病 Diseases	定义/特征 Definition/Characteristics	秀丽隐杆线虫模型 Caenorhabditis elegans models
杜氏肌营养不良症 Duchenne muscular dystrophy (DMD)	X染色体连锁隐性遗传，肌肉纤维逐渐坏死和假性肥大	dys-1; ace-1^[12]
肢带型肌营养不良 Limb-girdle muscular dystrophy (LGMD)	累及肩胛带与骨盆带，表现为对称性近端肌无力	LS587; giv otIs117^[13]
肌少症 Sarcopenia	衰老引起的骨骼肌质量显著减少，力量减弱	PD2856; PD2859; PD4092^[14];WJA780^[15]
线粒体肌病 Mitochondrial myopathies	线粒体功能障碍引起的骨骼肌病变	dct-1; allo-1^[16]
糖原累积病 Glycogen storage diseases	酶缺陷导致糖原异常积聚，常见于婴幼儿	RT258;VK2882; pwIs50^[17]
视网膜色素变性 Retinitis pigmentosa (RP)	感光细胞退化，以夜盲和视野缩小为早期表现	snrp-200; prp-8^[18]
骨质疏松症 Osteoporosis	骨密度下降，骨小梁破坏，易致脆性骨折	无
马凡综合征 Marfan syndrome	FBN1基因突变致结缔组织发育异常，累及骨、心血管、眼等系统	无
家族黑蒙性痴呆症 Tay-Sachs disease	HEXA基因突变，溶酶体中GM2神经节苷脂异常积聚	无
脊髓小脑性共济失调 Spinocerebellar ataxia	以共济失调为主要表现的常染色体显性遗传病	无
尼曼-皮克病 Niemann-Pick disease	脂类代谢障碍致肝脾大和神经系统损害	无
阿尔茨海默病 Alzheimer's disease (AD)	β淀粉样蛋白沉积和tau蛋白异常磷酸化引起的认知功能持续退化	Aβ₁_-₄₂^[19]
帕金森病 Parkinson's disease (PD)	黑质多巴胺能神经元丢失，表现为震颤、运动迟缓等	P301L；V337M^[20]；A53T^[21]
亨廷顿病 Huntington's disease (HD)	HTT基因CAG重复扩增引起基底节神经元退化，表现为舞蹈样运动和精神症状	HTN-Q150^[22]
肌萎缩侧索硬化 Amyotrophic lateral sclerosis (ALS)	上下运动神经元退化，导致肌肉萎缩、瘫痪	G93A SOD1^[23]
进行性核上性麻痹 Progressive supranuclear palsy	以垂直眼动障碍、姿势不稳和额叶认知障碍为特征的tau蛋白病	无
多发性硬化症 Multiple sclerosis	中枢神经系统白质脱髓鞘，伴随神经功能缺失	无