Table 3.
Neurological disorders in which abnormalities of the cytoskeleton appear as a secondary pathophysiological mechanism.
| Disease Name | Protein (UniProt Code)/Gene Name | Mutation | A brief Description of the Observations | Reference |
|---|---|---|---|---|
| Friedreich’s ataxia (FRDA)/OMIM #229300 | Frataxin (Q16595)/FXN | GAA-triplet repeats expansion or point mutations in the FXN gene. | The lack of frataxin produces a reduced spreading of vimentin, increment glutathionylation of actin and MT, increment of tyrosinated tubulin and irregular distribution of phosphorylated NF-H | [248,249,250,251] |
| Forms of Charcot-Marie-Tooth (CMT) neuropathy: Axonal recessive (AR-CMT2-OMIM#607706#608340), axonal dominant (CMT2K-OMIM#607831) and demyelinating recessive (CMT4A-OMIM#214400) | Ganglioside-induced differentiation-associated protein 1 (Q8TB36)/GDAP1 | Point mutations in the GDAP1 gene. | Decreased acetylation in α-tubulin. | [252] |
| Axonal dominant (CMT2F-OMIM#606595) form of Charcot-Marie-Tooth (CMT) neuropathy. | Heat shock protein beta-1 (P04792)/HSPB1 | p.S135F | Decreased acetylation in α-tubulin. | [253] |
| Sporadic Alzheimer Disease (sAD) | N/A * | Sporadic Alzheimer disease (SAD) has a variety of initiating factors. | Accumulation of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques that accumulate in vulnerable brain regions. The hyperphosphorylation of tau and other post-translational modifications (polyglutamylation, tyrosination and detyrosination) results in microtubule destabilization and cytoskeleton abnormalities, such as actin rods are related with the axonal degeneration underlying the pathophysiology of the AD. | [254,255,256,257,258] |
| Familial Alzheimer Disease (fAD)/OMIM #104300 | Amyloid B-protein (P05067)/APP; Presenilin-1(P49768)/PSEN1; Presenilin-2 (P49810)/PSEN2; | Familial Alzheimer Disease (fAD) is a genetically heterogeneous disorder. | ||
| Sporadic Parkinson Disease (sPD) | N/A * | Sporadic Parkinson Disease (SAD) has a variety of initiating factors. | Reduced microtubule stability, mass and imbalance in the pattern of tubulin post-translational modifications and associated proteins. This aberrant stability results in deregulation of axonal transport, including trafficking of mitochondria in neurons. | [259,260,261,262,263,264] |
| Familial Parkinson Disease (fPD) | 27 causative genes associated with PD | Familial Parkinson Disease (fAD) is a genetically heterogeneous disorder. | ||
| Huntington’s disease (HD)/ OMIM #143100 |
Huntingtin (P43858)/HTT | Expansion of CAG repeats in the HTT gene |
Alternative splicing is impaired in HD, altering microtubule-associated protein such as TAU and MAP2. | [265] |
| Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph Disease/OMIM#109150 | Ataxin-3 (P54252)/ATXN3 | Expanded CAG repeats | Expanded PolyQ protein disrupts a neuronal actin cytoskeleton. | [266] |
| Creutzfeldt-Jakob disease (CJD)/OMIM#123400 | Major prion protein (PrP) (P04156)/PRNP | p.P102L, p.V180I, p.E200K | Tau and NF-L concentrations are increased in the plasma of CJD patients. Synaptic abnormalities and Cofilin phosphorylation upregulated in the terminal stage of the disease. | [267,268] |
| Lowe syndrome/OMIM#309000 | Oculo-cerebro-renal syndrome Lowe 1(OCRL)(Q01968)/OCRL1 | Point mutations or deletions in the OCRL1 gene. | Abnormal F-actin dynamics in interphase cells affect endocytic recycling. | [267,268] |
| Lissencephaly-1/OMIM#607432 | Lissencephaly-1 (LIS1)(P43034)/PAFAH1B1 | Point mutations or deletions in the PAFAH1B1 gene. | Reduced Lis-1 expression in mice model of Lissencephaly 1 shows severe neuronal migration defects. | [237] |
* N/A, non-applicable; no proteins are listed since this is a multifactorial disease.