Table 2.

Cytoskeletal proteins and their mutations associated with neurological diseases as primary causes.

Protein (UniProt Code)/Gene Name	Mutation	Disease Name	A Brief Description of the Observations	References
Profilin (P07737)/PFN1	p.C71G, p.M114T, p.G118V, p.E118V, p.A20T, p.Q139L, p.T109M	Familial Amyotrophic Lateral Sclerosis (fALS)/OMIM # 105400	Mutations in PFN-1 form insoluble ubiquitinated agregates and show defects in growth cone morphology with altered actin levels.	[230,231]
	p.R136W, p.E117G, p.G15G	Sporadic Amyotrophic Lateral Sclerosis (sALS)/OMIM # 105400		[231,232,233]
β-III-Spectrin (O15020)/SPTBN2	p.L253P	Spinocerebellar ataxia type 5 (SCA5)/OMIM# 600224	The L253P mutant β-spectrin induces high-affinity binding that decreases spectrin-actin dynamics and consequently may alter the growing or remodelling of dendritic branches and spines.	[234]
Tubulin beta-2A chain (Q13885)/TUBB2A	p.D417N	TUBB2A progressive spastic ataxia syndrome	The D417N produces impaired binding to KIF1A, a neuron-specific kinesin required for transport of synaptic vesicle precursors.	[235]
Tubulin beta-4B chain (P04350)/TUBB4AB	p.R391H, p.R391C	Leber congenital amaurosis (LCA) with early-onset deafness/OMIM# 61789	The mutations in TUBB4B altered the dynamics of growing MTs.	[236]
Tubulin alfa-1A chain (Q71U36)/TUBA1A	Point mutations in the TUBA1A gene.	Lissencephaly-3/OMIM#611603	Mutations in Tubulin alfa-1A chain involve neuron migration defect, as a result, lead to brain malformations	[237]
Microtubule-associated protein tau (P10636)/MAPT	More than 40 pathological mutations	Primary tauopathies/OMIM # 157140	Post-translational modifications or unbalance of tau isoforms leading to intracellular inclusions in neurons and/or glia, promoting degeneration	[163]
Neurofilament light (P07196)/NEFL	p.P8R, p.P22S, p.N98S, p.E396K	Charcot-Marie-Tooth disease type 1F (CMT1F)/OMIM# 607734; Type 2E (CMT2E)/OMIM# 607684	A large number of NEFL mutations, localize along the gene, have been reported. Nevertheless, exist four common mutations clustered in three mutational hotspots. The pathogenic mechanism is different for each mutation in NFEL gene. The axonal maintenance is compromised cause to the neurofilament network, and axonal transport is altered.	[238]
Inverted formin-2 (Q27J81)/INF2	p.L57P, p.L77R, p.L69_S72del, p.C104R, p.C104W, p.C104F, p.R106P, p.G114D, p.L128P, p.L132R, p.L165P, p.E184K	Charcot-Marie-Tooth Neuropathy with Focal Segmental Glomerulosclerosis (CMTDIE)/OMIM# 614455	Mutations in INF2 dysregulates actin-dependent processes, interfering with myelinitation and mitochondrial dynamics.	[239,240,241,242]
Dystonin (Q03001)/DST	p.A203E; p.K4330Ter; p.E4955*; p.R206W; p.K229fs*21	Hereditary sensory autonomic neuropathy type VI (HSANVI)/OMIM# 614653	Variants of dystonin lead to abnormal actin cytoskeleton organization in fibroblast of patiens entails an alteration of cell adhesion and migration.	[204,243,244]
MACF1(Q9UPN3)/MACF1	p.C7135F; p.D7186Y; p.C7188F; p.C7188G; p.G6664R	Lissencephaly-9/OMIM#618325	MACF1, depending of variants cause defects in neuronal migration or axonal pathfinding or both.	[245]
Plectin (Q15149)/PLEC	Point mutations in the PLEC gene.	Epidermolysis bullosa simplex with muscular dystrophy/OMIM#226670	Patients shown lost of myelin of intramuscular nerves and signs of cerebellar and cerebral atrophy have been described.	[246,247]