Tubulinopathies and Their Brain Malformation Syndromes: Every TUB on Its Own Bottom

Nervous tissue is a vital component of the human body's communication system, enabling us to perceive and respond to stimuli. However, like all other tissues, it is vulnerable to disorders and diseases that can significantly impact our neurological functioning.
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...

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 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...

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...

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...