Protein and Water Contents of Aging Brain

Iz, Nagy; Nagy, Katalin; Lustyik, György

doi:10.1007/978-3-642-68507-1_15

Cited by 14 publications

(10 citation statements)

References 15 publications

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“…proteasomal clearance) and reduction in cell volume (e.g. loss of cellular and tissue water) (55)(56)(57). This would be the equivalent to increase volume occupancy by macromolecules, which may promote disease depending on the amyloid species being favored and/or stabilized.…”

Section: Discussionmentioning

confidence: 99%

Combined Effects of Agitation, Macromolecular Crowding, and Interfaces on Amyloidogenesis

Lee

Bird

Shaw

et al. 2012

Journal of Biological Chemistry

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Background: Macromolecular crowding and hydrophobic-hydrophilic interfaces promote amyloidogenesis. Results: The outcome of macromolecular crowding on A␤ amyloidogenesis depends on the spatial heterogeneity of the system. Conclusion: Viscosity dominates over the excluded volume effect only when the system contains a hydrophobic-hydrophilic interface. Significance: Studying both interfacial and macromolecular crowding effects together is crucial to understand amyloid systems in a physiological context.

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Section: Discussionmentioning

confidence: 99%

Combined Effects of Agitation, Macromolecular Crowding, and Interfaces on Amyloidogenesis

Lee

Bird

Shaw

et al. 2012

Journal of Biological Chemistry

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“…Agedependent cell volume changes have been measured in rat neurons; a 7% decrease in water content was detected by 30 months of age (29). Such a change in human brains would significantly increase the rates of R-synuclein protofibril and fibril formation.…”

Section: Discussionmentioning

confidence: 99%

“…This effect is nonspecific and can be sensitive to small fluctuations; one calculation predicts a 1 order of magnitude increase in the effective concentration based on an increase in the extent of crowding from 30 to 33% (28). Cell volumes fluctuate over a comparable range; a 7% decrease in neuronal volume has been observed in aged rats (29), and changes of 2-3-fold have been measured in Schwann cells progressing through the cell cycle (30). In addition to equilibrium constants, the rates of reactions for which the activation volume is negative are similarly increased.…”

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confidence: 97%

Molecular Crowding Accelerates Fibrillization of α-Synuclein: Could an Increase in the Cytoplasmic Protein Concentration Induce Parkinson's Disease?

2002

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Parkinson's disease (PD) is one of many neurodegenerative diseases that are characterized by amyloid fibril formation. Alpha-synuclein is a primary component of the fibrillar neuronal inclusions, known as Lewy bodies, that are diagnostic of PD. In addition, the alpha-synuclein gene is linked to familial PD. Fibril formation by alpha-synuclein proceeds via discrete beta-sheet-rich oligomers, or protofibrils, that are consumed as fibrils grow. Both FPD mutations accelerate formation of protofibrils, suggesting that these intermediates, rather than the fibril product, trigger neuronal loss. In idiopathic PD, other factors may be responsible for accelerating protofibril formation by wild-type alpha-synuclein. One possible factor could be molecular crowding in the neuronal cytoplasm. We demonstrate here that crowding using inert polymers significantly reduced the lag time for protofibril formation and the conversion of the protofibril to the fibril, but did not affect the morphology of either species. Physiologically realistic changes in the degree of in vitro crowding have significant kinetic consequences. Thus, nonspecific changes in the total cytoplasmic protein concentration, induced by cell volume changes and/or altered protein degradation, could promote formation of and stabilize the alpha-synuclein protofibril.

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“…All these evidences suggest that the increased incidence of amyloid disease in the aged persons may be a direct consequence of increased total intracellular protein concentration (or, equivalently, a decrease in cell-water content) in the cells of aging tissues. Interestingly, the water content in brain and liver cells are significantly decreased with advancing age [106][107][108] ultimately increasing the level of crowdedness in cells. We therefore, propose that with advancing age the pathogenesis of neurodegenerative disorders increases as a result of increase in the effective concentration of amyloidogenic proteins.…”

Section: Crowding Alters Protein Folding Leading To Aggregation: a Camentioning

confidence: 99%

Macromolecular crowding: Macromolecules friend or foe

Mittal

Chowhan

Singh

2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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Protein and Water Contents of Aging Brain

Cited by 14 publications

References 15 publications

Combined Effects of Agitation, Macromolecular Crowding, and Interfaces on Amyloidogenesis

Combined Effects of Agitation, Macromolecular Crowding, and Interfaces on Amyloidogenesis

Molecular Crowding Accelerates Fibrillization of α-Synuclein: Could an Increase in the Cytoplasmic Protein Concentration Induce Parkinson's Disease?

Macromolecular crowding: Macromolecules friend or foe

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