alpha-synuclein;
mathematical modelling;
Lewy body dementia;
Parkinson's disease;
neuron;
ALPHA-SYNUCLEIN;
PARKINSONS-DISEASE;
BODY FORMATION;
NUCLEATION;
MODEL;
D O I:
10.1093/imammb/dqac006
中图分类号:
Q [生物科学];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
This paper reports a minimal model simulating the growth of a Lewy body (LB). To the best of our knowledge, this is the first model simulating LB growth. The LB is assumed to consist of a central spherical core, which is composed of membrane fragments and various dysfunctional intracellular organelles, and a halo, which is composed of alpha-synuclein (alpha-syn) fibrils. Membrane fragments and alpha-syn monomers are assumed to be produced in the soma at constant rates. The growth of the core and the halo are simulated by the Finke-Watzky model. Analytical (closed-form) solutions describing the growth of the core and the halo are obtained. A sensitivity analysis in terms of model parameters is performed.
机构:
Washington Univ, Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, St Louis, MO 63108 USAWashington Univ, Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, St Louis, MO 63108 USA
机构:
Newcastle Gen Hosp, Dept Old Age Psychiat, Inst Hlth Elderly, Wolfson Res Ctr, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, EnglandNewcastle Gen Hosp, Dept Old Age Psychiat, Inst Hlth Elderly, Wolfson Res Ctr, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England
机构:
Massachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USAMassachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USA
Gómez-Tortosa, E
Ingraham, AO
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机构:
Massachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USAMassachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USA
Ingraham, AO
Irizarry, MC
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机构:
Massachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USAMassachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USA
Irizarry, MC
Hyman, BT
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机构:
Massachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USAMassachusetts Gen Hosp E, Alzheimers Dis Res Unit, Charlestown, MA 02119 USA
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Mayo, Mary Catherine
Bordelon, Yvette
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机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Movement Disorders Program, Los Angeles, CA 90095 USAUniv Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA