Modeling the Effect of Vesicle Traps on Mass Transfer and Traffic Jam Formation in Fast Axonal Transport

2010 ◽  
Author(s):  
Andrey V. Kuznetsov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mass Transfer ◽  
Neurodegenerative Diseases ◽  
Axonal Transport ◽  
Structural Changes ◽  
Molecular Motor ◽  
Fast Axonal Transport ◽  
Traffic Jam ◽  
The Right

This paper simulates effects of structural changes in the microtubule (MT) system on mass transfer in an axon. Understanding this process is important for understanding the underlying reasons for many neurodegenerative diseases, such as Alzheimer’s disease. In particular, it is investigated how the degree of polar mismatching in an MT swirl affects organelle trap regions in the axon and inhibiting transport of organelles down the axon. The model is based on modified Smith-Simmons equations governing molecular-motor-assisted transport in neurons. It is established that the structure that develops as a result of a region with disoriented MTs (the MT swirl) consists of two organelle traps, the trap to the left of the swirl region accumulates plus-end oriented organelles and the trap to the right of this region accumulates minus-end oriented organelles. The presence of such a structure is shown to decrease the transport of organelles toward the synapse of the axon. Four cases with a different degree of polar mismatching in the swirl region are investigated; the results are compared with simulations for a healthy axon, in which case organelle traps are absent.

Simulation of Traffic Jam Formation in Fast Axonal Transport

2009 ◽  
Author(s):  
A. V. Kuznetsov ◽  
A. A. Avramenko ◽  
D. G. Blinov
Keyword(s):  
Alzheimer’S Disease ◽  
Neurodegenerative Diseases ◽  
Axonal Transport ◽  
Tau Protein ◽  
Molecular Motors ◽  
Mechanistic Explanation ◽  
Fast Axonal Transport ◽  
Traffic Jam ◽  
Traffic Jams ◽  
Insight Into

Many neurodegenerative diseases, such as Alzheimer’s disease, are linked to swellings occurring in long arms of neurons. Many scientists believe that these swellings result from traffic jams caused by the failure of intracellular machinery responsible for fast axonal transport; such traffic jam can plug an axon and prevent the sufficient amount of organelles to be delivered toward the synapse of the axon. Mechanistic explanation of the formation of traffic jams in axons induced by overexpression of tau protein is based on the hypothesis that the traffic jam is caused not by the failure of molecular motors to transport organelles along individual microtubules but rather by the disruption of the microtubule system in an axon, by the formation of a swirl of disoriented microtubules at a certain location in the axon. This paper investigates whether a microtubule swirl itself, without introducing into the model microtubule discontinuities in the traffic jam region, is capable of capturing the traffic jam formation. The answer to this question can provide important insight into the mechanics of the formation of traffic jams in axons.

Modeling Bidirectional Transport of New and Used Organelles in Fast Axonal Transport in Neurons

2010 ◽  
Vol 133 (1) ◽  
Author(s):  
A. V. Kuznetsov
Keyword(s):  
Axonal Transport ◽  
Cell Body ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Fast Axonal Transport ◽  
Concentration Difference ◽  
Neuron Body ◽  
Microtubule Polarity ◽  
Bidirectional Transport ◽  
The Right

This paper develops a model for simulating transport of newly synthesized material from the neuron body toward the synapse of the axon as well as transport of misfolded and aggregated proteins back to the neuron body for recycling. The model demonstrates that motor-assisted transport, much similar to diffusion, can occur due to a simple concentration difference between the cell body and the synapse; organelles heading to the synapse do not need to attach preferably to plus-end-directed molecular motors, same as organelles heading to the neuron body for recycling do not need to attach preferably to minus-end-directed molecular motors. The underlying mechanics of molecular-motor-assisted transport is such that organelles would be transported to the right place even if new and used organelles had the same probability of attachment to plus-end-directed (and minus-end-directed) motors. It is also demonstrated that the axon with organelle traps and a region with a reversed microtubule polarity would support much smaller organelle fluxes of both new and used organelles than a healthy axon. The flux of organelles is shown to decrease as the width of organelle traps increases.

scholarly journals The Role of Mitochondria in Alzheimer's disease: Neurodegenerative Disease and Future Therapeutic Options

2018 ◽  
Vol 2 (1) ◽  
pp. 01-03
Author(s):  
Ruth Angale
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Structural Changes ◽  
Late Onset ◽  
Critical Role ◽  
Neuronal Loss ◽  
Ache Inhibitors ◽  
Age Related ◽  
Mitochondrial Oxidative Damage

Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal and clinical studies suggests that mitochondria play a critical role in aging, cancer, diabetes and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Several lines of research suggest that mitochondrial oxidative damage is an important cellular change in most late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and age-related diseases. In addition, epigenetic factors and lifestyle activities may contribute to selective disease susceptibility for each of these diseases. This paper discusses research that has elucidated features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases. This paper also discusses mitochondrial abnormalities and potential mitochondrial therapeutics in AD. Alzheimer's disease (AD) is characterized by neuronal loss and gradual cognitive impairment. AD is the leading cause of dementia worldwide and the incidence is increasing rapidly, with diagnoses expected to triple by the year 2050. Impaired cholinergic transmission is a major role player in the rapid deterioration associated with AD, primarily as a result of increased acetylcholinesterase (AChE) in the AD brain, responsible for reducing the amount of acetylcholine (ACh). Current drug therapies, known as AChE inhibitors (AChEIs), target this heightened level of AChE in an attempt to slow disease progression. AChEIs have only showed success in the treatment of mild to moderate AD symptoms, with the glutamate inhibitor memantine being the most common drug prescribed for the management of severe AD.

Fast Axonal Transport Misregulation and Alzheimer's Disease

2002 ◽  
Vol 2 (2) ◽  
pp. 089-100 ◽  
Author(s):  
Gerardo Morfini ◽  
Gustavo Pigino ◽  
Uwe Beffert ◽  
Jorge Busciglio ◽  
Scott T Brady
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axonal Transport ◽  
Fast Axonal Transport

Effect Of Nhexane Extract Of Caryota No Seed On Markers Of Neurodegeneration And Fecundity In Drosophila Melanogaster

2020 ◽  
Vol 6 (5) ◽  
pp. 1-7
Author(s):  
Chinonye A Maduagwuna ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drosophila Melanogaster ◽  
Neurodegenerative Diseases ◽  
Cognitive Functions ◽  
The Elderly ◽  
Common Cause ◽  
Chronic Neuroinflammation

Study background: Chronic neuroinflammation is a common emerging hallmark of several neurodegenerative diseases. Alzheimer’s Disease (AD) is the most common cause of dementia among the elderly and is characterized by loss of memory and other cognitive functions.

Sign in / Sign up

Export Citation Format

Share Document