Effects of Pathogenic Mutants of the Neuroprotective RNase 5-Angiogenin in Amyotrophic Lateral Sclerosis (ALS)

被引:0
作者
Gotte, Giovanni [1 ]
机构
[1] Univ Verona, Dept Neurosci Biomed & Movement Sci, Biol Chem Sect, Str La Grazie 8, I-37134 Verona, Italy
关键词
ALS; angiogenin; ribonucleases; RNase; 4; protein aggregation; amyloidosis; neurodegeneration; AMINO-ACID-SEQUENCE; BOVINE SEMINAL RIBONUCLEASE; SUPEROXIDE-DISMUTASE GENE; DOMAIN-SWAPPED DIMER; CRYO-EM STRUCTURES; HUMAN ANGIOGENIN; CRYSTAL-STRUCTURE; ANG GENE; 3-DIMENSIONAL STRUCTURE; PROTEIN AGGREGATION;
D O I
10.3390/genes15060738
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that affects the motoneurons. More than 40 genes are related with ALS, and amyloidogenic proteins like SOD1 and/or TDP-43 mutants are directly involved in the onset of ALS through the formation of polymorphic fibrillogenic aggregates. However, efficacious therapeutic approaches are still lacking. Notably, heterozygous missense mutations affecting the gene coding for RNase 5, an enzyme also called angiogenin (ANG), were found to favor ALS onset. This is also true for the less-studied but angiogenic RNase 4. This review reports the substrate targets and illustrates the neuroprotective role of native ANG in the neo-vascularization of motoneurons. Then, it discusses the molecular determinants of many pathogenic ANG mutants, which almost always cause loss of function related to ALS, resulting in failures in angiogenesis and motoneuron protection. In addition, ANG mutations are sometimes combined with variants of other factors, thereby potentiating ALS effects. However, the activity of the native ANG enzyme should be finely balanced, and not excessive, to avoid possible harmful effects. Considering the interplay of these angiogenic RNases in many cellular processes, this review aims to stimulate further investigations to better elucidate the consequences of mutations in ANG and/or RNase 4 genes, in order to achieve early diagnosis and, possibly, successful therapies against ALS.
引用
收藏
页数:22
相关论文
共 206 条
[1]   Structure- based design of nanobodies that inhibit seeding of Alzheimer's patient-extracted tau fibrils [J].
Abskharon, Romany ;
Pan, Hope ;
Sawaya, Michael R. ;
Seidler, Paul M. ;
Olivares, Eileen J. ;
Chen, Yu ;
Murray, Kevin A. ;
Zhang, Jeffrey ;
Lantz, Carter ;
Bentzel, Megan ;
Boyer, David R. ;
Cascio, Duilio ;
Nguyen, Binh A. ;
Hou, Ke ;
Cheng, Xinyi ;
Pardon, Els ;
Williams, Christopher K. ;
Nana, Alissa L. ;
V. Vinters, Harry ;
Spina, Salvatore ;
Grinberg, Lea T. ;
Seeley, William W. ;
Steyaert, Jan ;
Glabe, Charles G. ;
Loo, Rachel R. Ogorzalek ;
Loo, Joseph A. ;
Eisenberg, David S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2023, 120 (41)
[2]   Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation [J].
Abskharon, Romany ;
Sawaya, Michael R. ;
Boyer, David R. ;
Cao, Qin ;
Nguyen, Binh A. ;
Cascio, Duilio ;
Eisenberg, David S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2022, 119 (15)
[3]   CRYSTAL-STRUCTURE OF HUMAN ANGIOGENIN REVEALS THE STRUCTURAL BASIS FOR ITS FUNCTIONAL DIVERGENCE FROM RIBONUCLEASE [J].
ACHARYA, KR ;
SHAPIRO, R ;
ALLEN, SC ;
RIORDAN, JF ;
VALLEE, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :2915-2919
[4]   Loss of angiogenin function is related to earlier ALS onset and a paradoxical increase in ALS duration [J].
Aluri, Krishna C. ;
Salisbury, Joseph P. ;
Prehn, Jochen H. M. ;
Agar, Jeffrey N. .
SCIENTIFIC REPORTS, 2020, 10 (01)
[5]   PRINCIPLES THAT GOVERN FOLDING OF PROTEIN CHAINS [J].
ANFINSEN, CB .
SCIENCE, 1973, 181 (4096) :223-230
[6]   Molecular mechanisms in amyotrophic lateral sclerosis: the role of angiogenin, a secreted RNase [J].
Aparicio-Erriu, Isabela M. ;
Prehn, Jochen H. M. .
FRONTIERS IN NEUROSCIENCE, 2012, 6
[7]  
ARDELT W, 1991, J BIOL CHEM, V266, P245
[8]   Metal-free superoxide dismutase forms soluble oligomers under physiological conditions: A possible general mechanism for familial ALS [J].
Banci, Lucia ;
Bertini, Ivano ;
Durazo, Armando ;
Girotto, Stefania ;
Gralla, Edith Butler ;
Martinelli, Manuele ;
Valentine, Joan Selverstone ;
Vieru, Miguela ;
Whitelegge, Julian P. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (27) :11263-11267
[9]   Angiogenin Secretion From Hepatoma Cells Activates Hepatic Stellate Cells To Amplify A Self-Sustained Cycle Promoting Liver Cancer [J].
Barcena, Cristina ;
Stefanovic, Milica ;
Tutusaus, Anna ;
Martinez-Nieto, Guillermo A. ;
Martinez, Laura ;
Garcia-Ruiz, Carmen ;
de Mingo, Alvaro ;
Caballeria, Juan ;
Fernandez-Checa, Jose C. ;
Mari, Montserrat ;
Morales, Albert .
SCIENTIFIC REPORTS, 2015, 5
[10]   Deposition diseases and 3D domain swapping [J].
Bennett, Melanie J. ;
Sawaya, Michael R. ;
Eisenberg, David .
STRUCTURE, 2006, 14 (05) :811-824