F-box only protein 7 (FBXO7) is involved in the ubiquitination process during protein degradation. FBXO7 is a subunit of the SCF (SKP1/cullin‐1/F‐box protein) complex. The scaffold proteins cullin‐1 and SKP1, the RING subunit Rbx1 together with the substrate‐recruiting subunit FBXO7 form a functional E3 ubiquitin ligase. FBXO7 is implicated in Parkinson’s disease. In addition to reduced proteasome activity, loss of FBXO7 in mice leads to Parkinsonism-like phenotype. Human FBXO7 is mainly localized to the nucleus, while the mutation observed in patients with parkinsonian-pyramidal syndrome leads to impaired nuclear localization of this protein.

F-box only protein 7 (FBXO7) is involved in the ubiquitination process during protein degradation. FBXO7 is a subunit of the SCF (SKP1/cullin‐1/F‐box protein) complex. The scaffold proteins cullin‐1 and SKP1, the RING subunit Rbx1 together with the substrate‐recruiting subunit FBXO7 form a functional E3 ubiquitin ligase. FBXO7 is implicated in Parkinson’s disease. In addition to reduced proteasome activity, loss of FBXO7 in mice leads to Parkinsonism-like phenotype. Human FBXO7 is mainly localized to the nucleus, while the mutation observed in patients with parkinsonian-pyramidal syndrome leads to impaired nuclear localization of this protein.

PAK2 (p21-activated kinase 2) is a serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. It acts as the downstream effector of the small GTPases CDC42 and RAC1. PAK2 stimulates cell survival and cell growth, and knockdown of PAK2 induces cell cycle arrest. PAK2 is also implicated in the immune system. Loss of PAK2 results in reduced expression of multiple Treg functional molecules, including Foxp3, CD25, Nrp-1 and CTLA-4, coupled with a loss of Treg suppressive function in vitro and in vivo. The p21-activated kinases (PAKs) are the main effectors for the small Rho GTPases, critically involved in neurodevelopment, plasticity and maturation of the nervous system.

PAK2 (p21-activated kinase 2) is a serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. It acts as the downstream effector of the small GTPases CDC42 and RAC1. PAK2 stimulates cell survival and cell growth, and knockdown of PAK2 induces cell cycle arrest. PAK2 is also implicated in the immune system. Loss of PAK2 results in reduced expression of multiple Treg functional molecules, including Foxp3, CD25, Nrp-1 and CTLA-4, coupled with a loss of Treg suppressive function in vitro and in vivo. The p21-activated kinases (PAKs) are the main effectors for the small Rho GTPases, critically involved in neurodevelopment, plasticity and maturation of the nervous system.

Microglia are the resident parenchymal myeloid cells of the CNS, and play an important role in development, homeostasis, disease, and injury. TMEM119 is a transmembrane protein and was identified as a microglia-specific marker in both mouse and human CNS. Moreover, TMEM119 immunoreactivity has been exclusively detected on a subset of Iba1(+) CD68(+) microglia with ramified and amoeboid morphologies in the brains of neurodegenerative diseases. TMEM119 also plays an important role in bone formation and normal bone mineralization. It promotes the differentiation of myoblasts into osteoblasts. and it may induce the commitment and differentiation of myoblasts into osteoblasts. TMEM119 is also essential for normal spermatogenesis and late testicular differentiation.

Microglia are the resident parenchymal myeloid cells of the CNS, and play an important role in development, homeostasis, disease, and injury. TMEM119 is a transmembrane protein and was identified as a microglia-specific marker in both mouse and human CNS. Moreover, TMEM119 immunoreactivity has been exclusively detected on a subset of Iba1(+) CD68(+) microglia with ramified and amoeboid morphologies in the brains of neurodegenerative diseases. TMEM119 also plays an important role in bone formation and normal bone mineralization. It promotes the differentiation of myoblasts into osteoblasts. and it may induce the commitment and differentiation of myoblasts into osteoblasts. TMEM119 is also essential for normal spermatogenesis and late testicular differentiation.

ATF6 encodes a transcription factor that is anchored in the endoplasmic reticulum (ER) and activated during the unfolded protein response (UPR) to protect cells from ER stress. Under conditions of ER stress, ATF6 is transported from the ER to the Golgi apparatus, where it is cleaved by Golgi-resident proteases to release the cytosolic DNA-binding portion. Then the processed ATF6 moves to the nucleus to activate gene expression. Deletion of the isoform activating transcription factor 6α (ATF6α) and its paralog ATF6β results in embryonic lethality and notochord dysgenesis in nonhuman vertebrates, and loss-of-function mutations in ATF6α are associated with malformed neuroretina and congenital vision loss in humans. Altered ATF6 function in neurodegenerative disorders such as  Parkinson's disease has been observed. 

ATF6 encodes a transcription factor that is anchored in the endoplasmic reticulum (ER) and activated during the unfolded protein response (UPR) to protect cells from ER stress. Under conditions of ER stress, ATF6 is transported from the ER to the Golgi apparatus, where it is cleaved by Golgi-resident proteases to release the cytosolic DNA-binding portion. Then the processed ATF6 moves to the nucleus to activate gene expression. Deletion of the isoform activating transcription factor 6α (ATF6α) and its paralog ATF6β results in embryonic lethality and notochord dysgenesis in nonhuman vertebrates, and loss-of-function mutations in ATF6α are associated with malformed neuroretina and congenital vision loss in humans. Altered ATF6 function in neurodegenerative disorders such as  Parkinson's disease has been observed. 

ATF6 encodes a transcription factor that is anchored in the endoplasmic reticulum (ER) and activated during the unfolded protein response (UPR) to protect cells from ER stress. Under conditions of ER stress, ATF6 is transported from the ER to the Golgi apparatus, where it is cleaved by Golgi-resident proteases to release the cytosolic DNA-binding portion. Then the processed ATF6 moves to the nucleus to activate gene expression. Deletion of the isoform activating transcription factor 6α (ATF6α) and its paralog ATF6β results in embryonic lethality and notochord dysgenesis in nonhuman vertebrates, and loss-of-function mutations in ATF6α are associated with malformed neuroretina and congenital vision loss in humans. Altered ATF6 function in neurodegenerative disorders such as Parkinson's disease has been observed. 

ATF6 encodes a transcription factor that is anchored in the endoplasmic reticulum (ER) and activated during the unfolded protein response (UPR) to protect cells from ER stress. Under conditions of ER stress, ATF6 is transported from the ER to the Golgi apparatus, where it is cleaved by Golgi-resident proteases to release the cytosolic DNA-binding portion. Then the processed ATF6 moves to the nucleus to activate gene expression. Deletion of the isoform activating transcription factor 6α (ATF6α) and its paralog ATF6β results in embryonic lethality and notochord dysgenesis in nonhuman vertebrates, and loss-of-function mutations in ATF6α are associated with malformed neuroretina and congenital vision loss in humans. Altered ATF6 function in neurodegenerative disorders such as Parkinson's disease has been observed. 

Synaptotagmin-3 (SYT3)  is a member of the synaptotagmin family, which consists of 13  membrane trafficking proteins that contain a N-terminal transmembrane region, and two cytoplasmic C2 domains. Synaptotagmin-3 is mainly localized at the presynaptic terminals in the central nervous system, where it functions as a Ca2+ sensor and plays an important role in exocytosis of secretory vesicles and neurotransmitter release. It has been shown that Ca2+ influx triggers the interaction between the C2-domains of SYT3 and the phospholipid membranes.

Synaptotagmin-3 (SYT3)  is a member of the synaptotagmin family, which consists of 13  membrane trafficking proteins that contain a N-terminal transmembrane region, and two cytoplasmic C2 domains. Synaptotagmin-3 is mainly localized at the presynaptic terminals in the central nervous system, where it functions as a Ca2+ sensor and plays an important role in exocytosis of secretory vesicles and neurotransmitter release. It has been shown that Ca2+ influx triggers the interaction between the C2-domains of SYT3 and the phospholipid membranes.

The autophagy-lysosomal pathway is involved in the degradation of long-lived proteins. The transcription factor EB (TFEB) plays a critical role in regulating basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation. TFEB is also involved in the clearence if intracellular pathogenic targets in a variety of diseases, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity.

The autophagy-lysosomal pathway is involved in the degradation of long-lived proteins. The transcription factor EB (TFEB) plays a critical role in regulating basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation. TFEB is also involved in the clearence if intracellular pathogenic targets in a variety of diseases, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity.

Nicastrin is one of the essential components of the γ-secretase complex. The γ-secretase complex is one of the proteases involved in processing amyloid precursor protein (APP) to amyloid beta (Aβ). Nicastrin is not catalytically active, instead, it promotes the maturation and localization of other catalytic and regulatory units of the γ-secretase complex. Nicastrin has alsp been reported to regulate neprilysin, which is the enzyme involved in the degradation of Aβ fragment.

Nicastrin is one of the essential components of the γ-secretase complex. The γ-secretase complex is one of the proteases involved in processing amyloid precursor protein (APP) to amyloid beta (Aβ). Nicastrin is not catalytically active, instead, it promotes the maturation and localization of other catalytic and regulatory units of the γ-secretase complex. Nicastrin has alsp been reported to regulate neprilysin, which is the enzyme involved in the degradation of Aβ fragment.

TPP1 is a member of the sedolisin family of serine proteases. The proenzyme is activated in the lysosome by auto-proteolysis where it cleaves tripeptides from the N-termini of substrates. Mutations of TPP1 are associated with late-infantile neuronal ceroid lipofuscinosis and Spinocerebellar Ataxia, Autosomal Recessive 7.

TPP1 is a member of the sedolisin family of serine proteases. The proenzyme is activated in the lysosome by auto-proteolysis where it cleaves tripeptides from the N-termini of substrates. Mutations of TPP1 are associated with late-infantile neuronal ceroid lipofuscinosis and Spinocerebellar Ataxia, Autosomal Recessive 7.

Sortilin was originally purified from human brain tissue and was identified as a new lipoprotein receptor, which was later identified as a multifunctional sorting receptor of the VPS10P-domain receptor family. Although Sortilin is predominately expressed in neurons of the central and the peripheral nervous systems, it is also expressed in metabolic tissues including liver. Sortilin functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Sortilin is critical for lipid metabolism, and it has been implicated in lipid disorders. Sortilin is also an APOE receptor implicated in Alzheimer disease.

Sortilin was originally purified from human brain tissue and was identified as a new lipoprotein receptor, which was later identified as a multifunctional sorting receptor of the VPS10P-domain receptor family. Although Sortilin is predominately expressed in neurons of the central and the peripheral nervous systems, it is also expressed in metabolic tissues including liver. Sortilin functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Sortilin is critical for lipid metabolism, and it has been implicated in lipid disorders. Sortilin is also an APOE receptor implicated in Alzheimer disease.