Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative disease and therapeutics.
Axon-guidance-pathway molecules are involved in connectivity and repair throughout life (beyond guiding brain wiring during fetal development). One study found that variations (single-nucleotide polymorphisms [SNPs]) in axon-guidance-pathway genes were predictive of three Parkinson's disease (PD) outcomes (susceptibility, survival free of PD and age at onset of PD) in genome-wide association (GWA) datasets. The axon-guidance-pathway genes DCC, EPHB1, NTNG1, SEMA5A and SLIT3 were represented by SNPs predicting PD outcomes. Beyond GWA analyses, we also present relevant neurobiological roles of these axon-guidance-pathway molecules and consider mechanisms by which abnormal axon-guidance-molecule signaling can cause loss of connectivity and, ultimately, PD. Novel drugs and treatments could emerge from this new understanding.
Lin
Ling
L
Neuroregeneration Laboratories, Mailman Research Center, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. llin@mclean.harvard.edu
Lesnick
Timothy G
TG
Maraganore
Demetrius M
DM
Isacson
Ole
O
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D006801:Humans; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009474:Neurons / Q000473:pathology*; D013569:Synapses / Q000502:physiology*