Brain polyamine levels are altered in Alzheimer's disease

Morrison, Lesley D.; Kish, Stephen J.

doi:10.1016/0304-3940(95)11881-v

Cited by 119 publications

(96 citation statements)

References 18 publications

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“…We have recently shown that cells with non-functional NPC1 were more susceptible to the toxic effects of an endogenous lysosomal, membraneimpermeant polyamine metabolite (3-aminopropanal), relative to wild type cells. 3-Aminopropanal has been previously shown to be a potent neurotoxin implicated in neurodegenerative disorders (43)(44)(45)(46). It is thought to cause its toxic effects through its ability to react with and disrupt lysosomal membranes once sequestered in this compartment.…”

Section: Discussionmentioning

confidence: 99%

Niemann-Pick C1 Functions Independently of Niemann-Pick C2 in the Initial Stage of Retrograde Transport of Membrane-impermeable Lysosomal Cargo

Goldman

Krise

2010

Journal of Biological Chemistry

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The rare neurodegenerative disease Niemann-Pick Type C (NPC) results from mutations in either NPC1 or NPC2, which are membrane-bound and soluble lysosomal proteins, respectively. Previous studies have shown that mutations in either protein result in biochemically indistinguishable phenotypes, most notably the hyper-accumulation of cholesterol and other cargo in lysosomes. We comparatively evaluated the kinetics of [ 3 H]dextran release from lysosomes of wild type, NPC1, NPC2, and NPC1/NPC2 pseudo-double mutant cells and found significant differences between all cell types examined. Specifically, NPC1 or NPC2 mutant fibroblasts treated with NPC1 or NPC2 siRNA (to create NPC1/NPC2 pseudo-double mutants) secreted dextran less efficiently than did either NPC1 or NPC2 single mutant cell lines, suggesting that the two proteins may work independently of one another in the egress of membrane-impermeable lysosomal cargo. To investigate the basis for these differences, we examined the role of NPC1 and NPC2 in the retrograde fusion of lysosomes with late endosomes to create so-called hybrid organelles, which is believed to be the initial step in the egress of cargo from lysosomes. We show here that cells with mutated NPC1 have significantly reduced rates of late endosome/lysosome fusion relative to wild type cells, whereas cells with mutations in NPC2 have rates that are similar to those observed in wild type cells. Instead of being involved in hybrid organelle formation, we show that NPC2 is required for efficient membrane fission events from nascent hybrid organelles, which is thought to be required for the reformation of lysosomes and the release of lysosomal cargo-containing membrane vesicles. Collectively, these results suggest that NPC1 and NPC2 can function independently of one another in the egress of certain membrane-impermeable lysosomal cargo.

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Section: Discussionmentioning

confidence: 99%

Niemann-Pick C1 Functions Independently of Niemann-Pick C2 in the Initial Stage of Retrograde Transport of Membrane-impermeable Lysosomal Cargo

Goldman

Krise

2010

Journal of Biological Chemistry

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“…No significant influence of aging (1 d)103 y) was found on either putrescine or spermine levels in autopsied occipital cortex. Spermidine levels, however, age-dependently increased markedly from birth, reaching maximal levels at 40 y, and then were maintained up to senescence (Morrison and Kish 1995).…”

Section: Issues In Case Matchingmentioning

confidence: 94%

“…The stabilities of some representative small-molecular-weight (small-MW) compounds in autopsy tissue are detailed in Table 1 (Sloviter and Connor 1977;Spokes and Koch 1978;Adolfsson et al 1979a,b;Francis et al 1987;Palmer et al 1987;Cooper et al 1988;Lowe et al 1988;Procter et al 1988;Morrison and Kish 1995). Note that several compounds of interest, including neuroactive peptides, are remarkably stable postmortem (Dawbarn et al 1984;Wender et al 1994).…”

Section: Biochemical Integritymentioning

confidence: 99%

“…*Spermidine levels were found to increase markedly from birth, reaching maximal levels at approximately 40 years of age, which were maintained up until senescence. 1 Adolfsson et al (1979b) Morrison and Kish (1995). mRNAs from frozen autopsy tissue retain sufficient integrity to be used as templates for protein synthesis in vitro Morrison and Griffin 1981;Sajdel-Sulkowska et al 1983Guillemette et al 1986;Johnson et al 1986;Perrett et al 1988;Langstrom et al 1989;Leonard et al 1991).…”

Section: Molecular Integritymentioning

confidence: 99%

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Biochemical and molecular studies using human autopsy brain tissue

Hynd

Lewohl

Scott

et al. 2003

Journal of Neurochemistry

221

171

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The use of human brain tissue obtained at autopsy for neurochemical, pharmacological and physiological analyses is reviewed. RNA and protein samples have been found suitable for expression profiling by techniques that include RT-PCR, cDNA microarrays, western blotting, immunohistochemistry and proteomics. The rapid development of molecular biological techniques has increased the impetus for this work to be applied to studies of brain disease. It has been shown that most nucleic acids and proteins are reasonably stable postmortem. However, their abundance and integrity can exhibit marked intra-and intercase variability, making comparisons between case-groups difficult. Variability can reveal important functional and biochemical information. The correct interpretation of neurochemical data must take into account such factors as age, gender, ethnicity, medicative history, immediate ante-mortem status, agonal state and post-mortem and post-autopsy intervals. Here we consider issues associated with the sampling of DNA, RNA and proteins using human autopsy brain tissue in relation to various ante-and postmortem factors. We conclude that valid and practical measures of a variety of parameters may be made in human brain tissue, provided that specific factors are controlled.

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“…In the brains of AD patients, observed levels of acrolein or spermine ( SPM ) are increased,19, 20 whereas spermidine ( SPD ) or putrescine levels are decreased 19. Recent reports also indicate that polyamines can promote amyloid‐β peptide 1–40 (Aβ40) fibrillization, which is implicated in the acceleration of the AD process 21…”

Section: Methodsmentioning

confidence: 99%