Tubulin State Determines Proteopathic Fate
Lathan Lucas1, My Diem Quan1, Josephine C Ferreon1
1Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, Texas, USA.
Cytoskeleton (Hoboken, N.J.)
|June 12, 2026
Summary
Tubulin and microtubules actively influence neurodegenerative protein behavior, preventing pathological aggregation. Disruptions in this system may drive disease progression and offer new therapeutic targets.
Area of Science:
- Neurobiology
- Cell Biology
- Biochemistry
Background:
- Neurodegenerative diseases are characterized by protein aggregation.
- Cytoskeletal disruption is often viewed as a secondary effect.
Purpose of the Study:
- To propose that tubulin and microtubules are active regulators of protein aggregation in neurodegeneration.
- To explore the role of protein-microtubule interactions in disease pathogenesis.
- To identify the tubulin/microtubule system as a therapeutic target and biomarker.
Main Methods:
- Review of recent evidence on tubulin-protein interactions.
- Theoretical modeling of protein binding equilibria.
- Consideration of implications for therapy and biomarker development.
Main Results:
- Tubulin can redirect disease-linked protein condensates away from pathological aggregation.
- Loss of productive protein-microtubule engagement promotes pathological interactions.
- Microtubule disruption can exacerbate neurodegenerative processes.
Conclusions:
- The tubulin/microtubule system is a key determinant of neurodegenerative protein fate.
- Dysfunctional protein-microtubule engagement contributes to disease progression and mixed pathologies.
- Targeting tubulin and microtubules offers potential therapeutic and diagnostic strategies.
Related Concept Videos
02:17Microtubule 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...
01:45Destabilization 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...
01:15Drugs 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...
01:42Microtubule 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...
01:23Microtubule Formation
Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation of...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...