Molecular pathways to neurodegeneration.
The molecular bases underlying the pathogenesis of neurodegenerative diseases are gradually being disclosed. One problem that investigators face is distinguishing primary from secondary events. Rare, inherited mutations causing familial forms of these disorders have provided important insights into the molecular networks implicated in disease pathogenesis. Increasing evidence indicates that accumulation of aberrant or misfolded proteins, protofibril formation, ubiquitin-proteasome system dysfunction, excitotoxic insult, oxidative and nitrosative stress, mitochondrial injury, synaptic failure, altered metal homeostasis and failure of axonal and dendritic transport represent unifying events in many slowly progressive neurodegenerative disorders.
Center for Neuroscience & Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA. ebossy-wetzel@burnham.org
Ella
E
Bossy-Wetzel
Robert
R
Schwarzenbacher
Stuart A
SA
Lipton
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D011489:Protein Denaturation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D000685:Serum Amyloid A Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D010455:Peptides; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D050486:Serotonin Plasma Membrane Transport Proteins; D000685:Serum Amyloid A Protein; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C493230:SLC6A4 protein, human; C097188:polyglutamine; C111567:parkin protein; C105131:PARK7 protein, human