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Table 1 List of the genes that were selected for qRT-PCR validation

From: Transcriptomic characterization of tissues from patients and subsequent pathway analyses reveal biological pathways that are implicated in spastic ataxia

Gene symbol Encoded protein Protein description
MME Neprilysin A zinc-dependent metalloprotease/one of the most prominent beta amyloid (Aβ) degrading enzymes [22, 23]. Previous association with a number of neurological disorders, including Friedreich’s ataxia (FRDA), Charcot-Marie Tooth (CMT), autosomal recessive distal hereditary motor neuropathy and autosomal dominant spinocerebellar ataxia with neuropathy [22,23,24]
HERC5 E3 ISG15–protein ligase Participates in mitophagy and autophagy regulation through its association with ISG15. Deregulation of these processes by ISG15 was described in ataxia telangiectasia and other neurodegenerative diseases [25, 26]. Altered mRNA expression of HERC5 identified in iPSCs and neurons of a patient with Parkinson disease (PD) [27], as well as in skeletal muscle of Duchenne muscular dystrophy (DMD) patients [28]
NTN1 Netrin-1 Belongs to the family of laminin-related secreted proteins. Under-expressed mRNA in the brain of mucopolysaccharidosis type II mouse models [29] and up-regulated protein in brain tissue and cerebrospinal fluid of Alzheimer disease (AD) patients and mouse models [30] previously identified
PARP14 poly (ADP-ribose) polymerase family member 14 A known anti-apoptotic protein with possible role in the monitoring of aerobic respiration [31]
PLSCR1 Phospholipid scramblase 1 Involved in the reorganization of the phospholipid bilayer of the plasma membrane. Its activation might result to increased phosphatidylserine levels at the plasma membrane, which is indicative of apoptotic or energy-deprived cells and αβ toxicity. Also implicated in calcium homeostasis in neuronal cells, as well as autophagy, and associated with AD and cancer [32, 33]
SERINC5 Serine incorporator 5 Involved in myelination. It adds serine into newly forming membrane lipids and is enriched in myelin in the brain [34]
PLD1 Phospholipase D1 Involved in the regulation of cytoskeleton organization in neurons, in dendritic branching and spine regulation. Downregulation of PLD1 has been described to affect α-synuclein-triggered neurodegeneration in PD [35]
NR4A3 Nuclear receptor subfamily 4, group A, member 3 Also known as neuron-derived orphan receptor-1. It is involved in various biological processes like the cell cycle, neuronal differentiation, apoptosis and metabolism. It can also act as a transcription factor. Its homolog NR4A2 has been previously linked to the pathogenesis of PD [36]
CYP7B1 Cytochrome P450 Family 7 Subfamily B Member 1 A protein of the cytochrome P450 superfamily of enzymes. CYP7B1 variants have been reported in pure and complex forms of hereditary spastic paraplegia 5, as well as bile acid metabolism disorder [37, 38]. The enzyme has a role in cholesterol metabolism and primary bile acid production and it is widely expressed in the liver and brain [37]
ADAM23 ADAM Metallopeptidase 23 A cell-surface glycoprotein expressed in CNS neurons [39]. It participates in several biological processes, such as myoblast differentiation, growth factor secretion and others, and has been shown to be dysregulated in PBMCs from classic ataxia telangiectasia patients [39, 40]. Also shown to have altered expression in blood and brain of PD patients [41]
STK17B Serine/Threonine Kinase 17b Acts as a positive regulator of apoptosis [42]. It has been suggested to promote carcinogenesis and metastasis through its involvement in the AKT/GSK-3β/Snail signaling pathway [43]
GLDC Glycine dehydrogenase Catalyses the breakdown of glycine, that is involved in fatty acid response, and has a protein homodimerization activity. It has been shown to undergo methylation alterations in aging [44], while variants of the gene were reported in cases of corticobasal degeneration, progressive supranuclear palsy and frontotemporal dementia [45]
SPG7 Paraplegin A mitochondrial metalloprotease with many reported variants causing SA, HSP or HCA. It disrupts mitochondrial dynamics and calcium homeostasis [46]. It is highly expressed in large neurons, such as cortical pyramidal neurons and Purkinje cells and associates with AFG3L2 to form a hetero-oligomeric complex. Variants of the AFG3L2 gene have been previously reported to cause spinocerebellar ataxia type 28 and autosomal recessive SA type 5 [47]
MTRNR2L1 Humanin-like protein 1 Neuroprotective and anti-apoptotic role in cortical neurons [48]