Related Experiment Video

Updated: Jun 12, 2026

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
08:24

A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model

Published on: November 25, 2022

Microtubule depolymerization potentiates alpha-synuclein oligomerization

A Raquel Esteves1, Daniela M Arduíno, Russell H Swerdlow

  • 1Centro de Neurociências e Biologia Celular, Universidade de Coimbra Portugal.

Frontiers in Aging Neuroscience
|June 17, 2010
PubMed

Insights

Mitochondrial dysfunction in Parkinson's disease (PD) may disrupt the cell's internal structure, promoting toxic alpha-synuclein clumps. Stabilizing microtubules with Taxol offers a potential therapeutic avenue for PD.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Parkinson's disease (PD) is characterized by mitochondrial dysfunction and alpha-synuclein aggregation.
  • The interplay between these pathological hallmarks remains incompletely understood.
  • Cytoskeletal integrity is crucial for neuronal function.

Purpose of the Study:

  • To investigate the mechanistic link between mitochondrial dysfunction and alpha-synuclein aggregation in a cellular model of Parkinson's disease.
  • To explore the role of the microtubule cytoskeleton in this process.

Main Methods:

  • Utilized a Parkinson's disease (PD) cytoplasmic hybrid (cybrid) cell line with patient-derived mitochondria.
  • Assessed cellular energetics (ATP levels), microtubule dynamics (tubulin ratio), and alpha-synuclein oligomerization.
  • Administered Taxol, a microtubule-stabilizing agent, to PD cybrid cells.

Main Results:

  • PD cybrid cells exhibited reduced ATP levels, increased free/polymerized tubulin ratio, and accumulated alpha-synuclein oligomers compared to controls.
  • Taxol treatment normalized the tubulin ratio and decreased alpha-synuclein oligomerization in PD cybrid cells.
  • These findings suggest mitochondrial dysfunction initiates cytoskeletal destabilization, promoting alpha-synuclein aggregation.

Conclusions:

  • A significant nexus exists between mitochondrial function, cytoskeleton homeostasis, and alpha-synuclein oligomerization in Parkinson's disease.
  • Mitochondrial dysfunction appears to trigger microtubule destabilization, which in turn promotes alpha-synuclein oligomerization.
  • Targeting microtubule dynamics may represent a novel therapeutic strategy for Parkinson's disease.
Keywords:
ATPParkinson diseasealpha-synucleincybridsmitochondriatubulin

More Related Videos

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation09:16

Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation

Published on: June 26, 2018

Quantitative Microtubule Fractionation Technique to Separate Stable Microtubules, Labile Microtubules, and Free Tubulin in Mouse Tissues07:21

Quantitative Microtubule Fractionation Technique to Separate Stable Microtubules, Labile Microtubules, and Free Tubulin in Mouse Tissues

Published on: November 17, 2023

Related Concept Videos

Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
Assembly of Complex Microtubule Structures01:32

Assembly of Complex Microtubule Structures

Complex microtubule structures are present in resting cells and in dividing cells. In resting cells, they are responsible for maintaining the cellular architecture, tracks for intracellular transport, positioning of organelles, assembly of cilia and flagella. They mediate the bipolar spindle assembly for chromosomal segregation and positioning of the cell division plate in dividing cells. The formation of microtubule complex structures depends on the cell type, cell stage, and cell function.
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...