The cytoskeleton is a three-dimensional structure in all eukaryotic cells and can therefore be found in neurons.
Although it does not differ much from the rest of somatic cells, The cytoskeleton of neurons has some characteristics of its own in addition to being important when they have defects, as is the case with Alzheimer’s disease.
Below we will see the three types of filaments that make up this structure, its particularities with respect to the rest of the cytoskeletons and how it is affected in Alzheimer’s.
The cytoskeleton is one of the defining elements of eukaryotic cells , that is, those that have a defined nucleus, a structure which can be observed in animal and plant cells. This structure is, in essence, the internal scaffolding on which the organelles are supported, organizing the cytosol and the vesicles found in it, such as lysosomes.
Neurons are eukaryotic cells specialized in forming connections with others and constituting the nervous system and, as with any other eukaryotic cell, neurons have a cytoskeleton. The cytoskeleton of the neuron, structurally speaking, is not very different from that of any other cell, possessing microtubules, intermediate filaments and actin filaments.
Below we will see each of these three types of filaments or tubes, specifying how the cytoskeleton of the neuron differs from that of other somatic cells.
Microtubules
Neuron microtubules are not very different from those found in other cells in the body. Its main structure consists of a polymer of 50-kDa tubulin subunits which is twisted in such a way that it forms a hollow tube with a diameter of 25 nanometers.
There are two types of tubulin: alpha and beta. Both are proteins not very different from each other, with a sequence similarity close to 40%. It is these proteins that constitute the hollow tube, through the formation of protofilaments that join together laterally, thus forming the microtubule.
Tubulin is an important substance, since Its dimers are responsible for joining two guanosine triphosphate (GTP) molecules , dimers which have the capacity to carry out enzymatic activity on these same molecules. It is through this GTPase activity that is involved in the formation (assembly) and disassembly (disassembly) of the microtubules themselves, giving flexibility and the capacity for modification to the cytoskeletal structure.
Axon microtubules and dendrites are not continuous with the cell body , nor are they associated with any visible MTOC (microtubule organizing center). Axonal microtubules can be 100 μm long, but have uniform polarity. In contrast, the microtubules of dendrites are shorter, presenting mixed polarity, with only 50% of their microtubules oriented towards the distal end of the cell body.
Although the microtubules of neurons are made up of the same components that can be found in the rest of the cells, it should be noted that they may present some differences. Brain microtubules contain tubulins of different isotypes, and with a variety of proteins associated with them. Besides, The composition of microtubules varies depending on the location within the neuron , such as axons or dendrites. This suggests that microtubules in the brain could specialize in different tasks, depending on the unique environments provided by the neuron.
Intermediate filaments
As with microtubules, intermediate filaments are components of both the neuronal cytostructure and that of any other cell. These filaments They play a very interesting role in determining the degree of specificity of the cell , in addition to being used as markers of cellular differentiation. In appearance, these filaments resemble a rope.
In the body there are up to five types of intermediate filaments, ordered from I to V and, some of them being those that can be found in the neuron:
Type I and II intermediate filaments are keratinous in nature and can be found in various combinations with epithelial cells of the body In contrast, type III can be found in less differentiated cells, such as glia cells or neuronal precursors, although they have also been seen in more formed cells, such as those that make up smooth muscle tissue and in astrocytes. mature.
Type IV intermediate filaments are specific to neurons, presenting a common pattern between exons and introns , which differ significantly from those of the previous three types. Type V are those found in the nuclear laminae, forming the part that surrounds the cell nucleus.
Although these five different types of intermediate filaments are more or less specific to certain cells, it is worth mentioning that the nervous system contains a diversity of these. Despite their molecular heterogeneity, all intermediate filaments in eukaryotic cells appear, as we had mentioned, as fibers reminiscent of a rope, with a diameter between 8 and 12 nanometers.
The neuronal filaments can be hundreds of micrometers in length, in addition to having projections in the form of lateral arms On the other hand, in other somatic cells, such as glia and non-neuronal cells, these filaments are shorter, lacking lateral arms.
The main type of intermediate filament that can be found in the myelinated axons of the neuron is formed by three protein subunits, forming a triplet: a high molecular weight subunit (NFH, 180 to 200 kDa), a low molecular weight subunit medium (NFM, 130 to 170 kDa) and a low molecular weight subunit (NFL, 60 to 70 kDa). Each protein subunit is encoded by a separate gene. These proteins are those that make up type IV filaments, which are expressed only in neurons and have a characteristic structure.
But although those of the nervous system are type IV, other filaments can also be found in it. Vimentin is one of the proteins that make up type III filaments , present in a wide variety of cells, including fibroblasts, microglia and smooth muscle cells. They are also found in embryonic cells, as precursors of glia and neurons. Astrocytes and Schwann cells contain acidic fibrillary glial protein, which constitutes type III filaments.
actin microfilaments
Actin microfilaments are the oldest components of the cytoskeleton They are formed by 43-kDa actin monomers, which are organized as if they were two strings of pearls, with diameters of 4 to 6 nanometers.
Actin microfilaments can be found in neurons and glial cells, but are especially concentrated in presynaptic terminals, dendritic spines, and neural growth cones.
What role does the neuronal cytoskeleton play in Alzheimer’s?
It has been found a relationship between the presence of beta-amyloid peptides, components of the plaques that accumulate in the brain in Alzheimer’s disease , and the rapid loss of dynamics of the neuronal cytoskeleton, especially in the dendrites, where the nervous impulse is received. As this part is less dynamic, the transmission of information becomes less efficient, in addition to decreasing synaptic activity.
In a healthy neuron, Its cytoskeleton is made up of actin filaments that, although anchored, have a certain flexibility To provide the necessary dynamism so that the neuron can adapt to the demands of the environment, there is a protein, cofilin 1, which is responsible for cutting the actin filaments and separating its units. Thus the structure changes from form to form, however, if cofilin 1 is phosphorylated, that is, a phosphorus atom is added, it stops working correctly.
It has been seen that exposure to beta-amyloid peptides induces greater phosphorylation of cofilin 1. This causes the cytoskeleton to lose dynamism, since the actin filaments are stabilized, and the structure loses flexibility. Dendritic spines lose function.
One of the causes that cause cofilin 1 to become phosphorylated is when the enzyme ROCK (Rho-kinase) acts on it This enzyme phosphorylates molecules, inducing or deactivating their activity, and would be one of the causes of Alzheimer’s symptoms, since it deactivates cofilin 1. To avoid this effect, especially during the early stages of the disease, there is the drug Fasucil, which inhibits the action of this enzyme and prevents cofilin 1 from losing its function.
