Convergent pathogenic pathways in Alzheimer’s and Huntington disease: Shared targets for drug development

BDNF and NGF levels are reduced in both HD and AD. Presynaptically, Htt, APP and Tau influence trafficking mechanisms via interaction with HAP1, kinesin and dynein/dynactin, influencing their binding to microtubules. Pro-BDNF and pro-NGF are processed by unknown proteases to generate mature BDNF and NGF. Furthermore, TrkA and TrkB receptor levels are decreased in AD and HD, respectively. Signalling through Trk receptors is reduced, thereby increasing Gsk3ß activity and enhancing cell death pathways. Increased p75NTR levels and signalling mediated by pro-BDNF and pro-NGF also triggers cell death. Therapeutics examined to date include: Epothilone D, BDNF, NGF, glucocorticoids and Lithium. Therapeutic targets are highlighted in red; Drugs are highlighted in green.
Convergent pathogenic pathways in Alzheimer’s and Huntington disease: Shared targets for drug development
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Convergent pathogenic pathways in Alzheimer’s and Huntington disease: Shared targets for drug development. () Dagmar E. Ehrnhoefer, et al. Nat Rev Drug Discov. ;10(11):853-867. Figure: F2.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Homo sapiens Primates HTT HTT ncbigene_symbol HTT 3064
Homo sapiens Primates HTT HTT ncbigene_synonym SLC6A4 6532
Homo sapiens Primates APP APP ncbigene_symbol APP 351
Homo sapiens Primates HAP1 HAP1 ncbigene_symbol HAP1 9001
Homo sapiens Primates HAP1 HAP1 ncbigene_synonym APEX1 328
Homo sapiens Primates kinesin KINESIN famplex_relations CENPE 1062
Homo sapiens Primates kinesin KINESIN famplex_relations KIF11 3832
Homo sapiens Primates kinesin KINESIN famplex_relations KIF12 113220
Homo sapiens Primates kinesin KINESIN famplex_relations KIF13A 63971
Homo sapiens Primates kinesin KINESIN famplex_relations KIF13B 23303
Homo sapiens Primates kinesin KINESIN famplex_relations KIF14 9928
Homo sapiens Primates kinesin KINESIN famplex_relations KIF15 56992
Homo sapiens Primates kinesin KINESIN famplex_relations KIF16B 55614
Homo sapiens Primates kinesin KINESIN famplex_relations KIF17 57576
Homo sapiens Primates kinesin KINESIN famplex_relations KIF18A 81930
Homo sapiens Primates kinesin KINESIN famplex_relations KIF18B 146909
Homo sapiens Primates kinesin KINESIN famplex_relations KIF19 124602
Homo sapiens Primates kinesin KINESIN famplex_relations KIF1A 547
Homo sapiens Primates kinesin KINESIN famplex_relations KIF1B 23095
Homo sapiens Primates kinesin KINESIN famplex_relations KIF1C 10749
Homo sapiens Primates kinesin KINESIN famplex_relations KIF20A 10112
Homo sapiens Primates kinesin KINESIN famplex_relations KIF20B 9585
Homo sapiens Primates kinesin KINESIN famplex_relations KIF21A 55605
Homo sapiens Primates kinesin KINESIN famplex_relations KIF21B 23046
Homo sapiens Primates kinesin KINESIN famplex_relations KIF22 3835
Homo sapiens Primates kinesin KINESIN famplex_relations KIF23 9493
Homo sapiens Primates kinesin KINESIN famplex_relations KIF24 347240
Homo sapiens Primates kinesin KINESIN famplex_relations KIF25 3834
Homo sapiens Primates kinesin KINESIN famplex_relations KIF26A 26153
Homo sapiens Primates kinesin KINESIN famplex_relations KIF26B 55083
Homo sapiens Primates kinesin KINESIN famplex_relations KIF27 55582
Homo sapiens Primates kinesin KINESIN famplex_relations KIF2A 3796
Homo sapiens Primates kinesin KINESIN famplex_relations KIF2B 84643
Homo sapiens Primates kinesin KINESIN famplex_relations KIF2C 11004
Homo sapiens Primates kinesin KINESIN famplex_relations KIF3A 11127
Homo sapiens Primates kinesin KINESIN famplex_relations KIF3B 9371
Homo sapiens Primates kinesin KINESIN famplex_relations KIF3C 3797
Homo sapiens Primates kinesin KINESIN famplex_relations KIF4A 24137
Homo sapiens Primates kinesin KINESIN famplex_relations KIF4B 285643
Homo sapiens Primates kinesin KINESIN famplex_relations KIF5A 3798
Homo sapiens Primates kinesin KINESIN famplex_relations KIF5B 3799
Homo sapiens Primates kinesin KINESIN famplex_relations KIF5C 3800
Homo sapiens Primates kinesin KINESIN famplex_relations KIF6 221458
Homo sapiens Primates kinesin KINESIN famplex_relations KIF7 374654
Homo sapiens Primates kinesin KINESIN famplex_relations KIF9 64147
Homo sapiens Primates kinesin KINESIN famplex_relations KIFC1 3833
Homo sapiens Primates kinesin KINESIN famplex_relations KIFC2 90990
Homo sapiens Primates kinesin KINESIN famplex_relations KIFC3 3801
Homo sapiens Primates kinesin KINESIN famplex_relations STARD9 57519
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC1H1 1778
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC1I1 1780
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC1I2 1781
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC1LI1 51143
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC1LI2 1783
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLL1 8655
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLL2 140735
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLRB1 83658
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLRB2 83657
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLT1 6993
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLT3 6990
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC2H1 79659
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC2LI1 51626
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLT2B 255758
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC2I1 55112
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNC2I2 89891
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAI7 55259
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH1 25981
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH10 196385
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH12 201625
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH14 127602
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH2 146754
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH3 55567
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH6 1768
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH7 56171
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAI3 126820
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAI4 79819
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH11 8701
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH17 8632
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH5 1767
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH8 1769
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAH9 1770
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAI1 27019
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAI2 64446
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAL1 83544
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DNAL4 10126
Homo sapiens Primates Dynein/dynactin DYNEIN famplex_relations DYNLT2 6991
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-8 619465
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-10 100616101
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-9 100616102
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-21 100616103
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-18 100775105
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-25 100862683
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-24 100862684
Homo sapiens Primates proteases PROTEASE ncbigene_synonym ERVK-19 105376906
Homo sapiens Primates Gsk3ß GSK3 famplex_relations GSK3A 2931
Homo sapiens Primates Gsk3ß GSK3 famplex_relations GSK3B 2932
Homo sapiens Primates NGF NGF ncbigene_symbol NGF 4803
Homo sapiens Primates BDNF BDNF ncbigene_symbol BDNF 627
Homo sapiens Primates BDNF BDNF ncbigene_synonym BDNF-AS 497258
Homo sapiens Primates TrkB TRKB ncbigene_synonym NTRK2 4915
Homo sapiens Primates TrkA TRKA ncbigene_synonym NTRK1 4914
Homo sapiens Primates P75NTR P75NTR ncbigene_synonym NGFR 4804
Homo sapiens Primates Akt AKT ncbigene_synonym AKT1 207
Homo sapiens Primates Akt AKT famplex_relations AKT2 208
Homo sapiens Primates Akt AKT famplex_relations AKT3 10000
Homo sapiens Primates PI3K/Akt PI3K ncbigene_synonym PIK3CA 5290
Homo sapiens Primates PI3K/Akt PI3K ncbigene_synonym PIK3CB 5291
Homo sapiens Primates PI3K/Akt PI3K ncbigene_synonym PIK3CD 5293
Homo sapiens Primates PI3K/Akt PI3K ncbigene_synonym PIK3CG 5294
Homo sapiens Primates PI3K/Akt PI3K famplex_relations PIK3R3 8503
Homo sapiens Primates PI3K/Akt PI3K famplex_relations PIK3R4 30849
Homo sapiens Primates PI3K/Akt PI3K famplex_relations PIK3R5 23533
Homo sapiens Primates PI3K/Akt PI3K famplex_relations PIK3R6 146850
Homo sapiens Primates PI3K/Akt PI3K famplex_relations PIK3R1 5295
Homo sapiens Primates PI3K/Akt PI3K famplex_relations PIK3R2 5296
Homo sapiens Primates red RED ncbigene_synonym IK 3550
Homo sapiens Primates red RED ncbigene_synonym DYRK3 8444
Mus musculus Rodents HTT HTT ncbigene_symbol Htt 15194
Mus musculus Rodents HTT HTT ncbigene_synonym Slc6a4 15567
Mus musculus Rodents APP APP ncbigene_symbol App 11820
Mus musculus Rodents HAP1 HAP1 ncbigene_symbol Hap1 15114
Mus musculus Rodents HAP1 HAP1 ncbigene_synonym Apex1 11792
Mus musculus Rodents Gsk3ß GSK3 ncbigene_synonym Gsk3b 56637
Mus musculus Rodents NGF NGF ncbigene_symbol Ngf 18049
Mus musculus Rodents BDNF BDNF ncbigene_symbol Bdnf 12064
Mus musculus Rodents TrkB TRKB ncbigene_synonym Ntrk2 18212
Mus musculus Rodents TrkA TRKA ncbigene_synonym Ntrk1 18211
Mus musculus Rodents P75NTR P75NTR ncbigene_synonym Ngfr 18053
Mus musculus Rodents Akt AKT ncbigene_synonym Akt1 11651
Mus musculus Rodents PI3K/Akt PI3K ncbigene_synonym Pik3r1 18708
Mus musculus Rodents red RED ncbigene_synonym Hmgcr 15357
Rattus norvegicus Rodents HTT HTT ncbigene_symbol Htt 29424
Rattus norvegicus Rodents APP APP ncbigene_symbol App 54226
Rattus norvegicus Rodents HAP1 HAP1 ncbigene_symbol Hap1 29430
Rattus norvegicus Rodents NGF NGF ncbigene_symbol Ngf 310738
Rattus norvegicus Rodents BDNF BDNF ncbigene_symbol Bdnf 24225
Rattus norvegicus Rodents TrkB TRKB ncbigene_synonym Ntrk2 25054
Rattus norvegicus Rodents P75NTR P75NTR ncbigene_synonym Ngfr 24596
Rattus norvegicus Rodents Akt AKT ncbigene_synonym Akt1 24185
Rattus norvegicus Rodents PI3K/Akt PI3K ncbigene_synonym Pik3cg 298947
Rattus norvegicus Rodents red RED ncbigene_synonym Ik 291659
Drosophila melanogaster Invertebrates and AND ncbigene_synonym CkIIbeta 32132
Drosophila melanogaster Invertebrates and AND ncbigene_synonym Andorra 32798
Drosophila melanogaster Invertebrates and AND ncbigene_synonym Anp 43595
Drosophila melanogaster Invertebrates and AND ncbigene_synonym Acam 44913
Drosophila melanogaster Invertebrates HTT HTT ncbigene_symbol htt 43392
Drosophila melanogaster Invertebrates APP APP ncbigene_symbol app 39399
Drosophila melanogaster Invertebrates APP APP ncbigene_synonym Appl 31002
Drosophila melanogaster Invertebrates APP APP ncbigene_synonym ApepP 35029
Drosophila melanogaster Invertebrates APP APP ncbigene_synonym APP-BP1 39244
Drosophila melanogaster Invertebrates kinesin KINESIN ncbigene_synonym Khc 36810
Drosophila melanogaster Invertebrates kinesin KINESIN ncbigene_synonym Klc 39445
Drosophila melanogaster Invertebrates Dynein/dynactin DYNEIN ncbigene_synonym Dhc64C 38580
Drosophila melanogaster Invertebrates Gsk3ß GSK3 ncbigene_synonym sgg 31248
Drosophila melanogaster Invertebrates Akt AKT ncbigene_symbol Akt 41957
Drosophila melanogaster Invertebrates PI3K/Akt PI3K ncbigene_synonym Pi3K21B 33203
Drosophila melanogaster Invertebrates PI3K/Akt PI3K ncbigene_synonym Pi3K59F 37733
Drosophila melanogaster Invertebrates PI3K/Akt PI3K ncbigene_synonym Pi3K68D 39329
Drosophila melanogaster Invertebrates PI3K/Akt PI3K ncbigene_synonym Pi3K92E 42446
Drosophila melanogaster Invertebrates red RED ncbigene_symbol red 41738
Drosophila melanogaster Invertebrates red RED ncbigene_synonym trc 40165
Danio rerio Vertebrates HTT HTT ncbigene_symbol htt 30214
Danio rerio Vertebrates APP APP ncbigene_synonym appa 58083
Danio rerio Vertebrates HAP1 HAP1 ncbigene_symbol hap1 100001887
Danio rerio Vertebrates Gsk3ß GSK3 ncbigene_synonym gsk3ba 30654
Danio rerio Vertebrates Gsk3ß GSK3 ncbigene_synonym gsk3ab 30664
Danio rerio Vertebrates NGF NGF ncbigene_synonym ngfb 58133
Danio rerio Vertebrates BDNF BDNF ncbigene_symbol bdnf 58118
Danio rerio Vertebrates TrkA TRKA ncbigene_synonym ntrk1 30546

Chemical mentions

Word Match MeSH Name ChEBI
Epothilone D NA mesh:C114026

Disease mentions

Word Match MeSH Name DOID