Risks and rewards of targeting NAD+ homeostasis in the brain

被引：8

作者：

Li, Catherine ^{[1
]}

Wu, Lindsay E. ^{[1
]}

机构：

[1] UNSW Sydney, Sch Med Sci, Sydney, NSW 2052, Australia

来源：

MECHANISMS OF AGEING AND DEVELOPMENT | 2021年 / 198卷

基金：

英国医学研究理事会;

关键词：

Nicotinamide adenine dinucleotide (NAD plus ); Neurodegeneration; SARM1; CD38; Therapeutics; ADP-RIBOSYL CYCLASE; NICOTINAMIDE MONONUCLEOTIDE; POLY(ADP-RIBOSE) POLYMERASE; ALZHEIMERS-DISEASE; MOUSE MODEL; DNA-DAMAGE; WALLERIAN DEGENERATION; RAT MODEL; MITOCHONDRIAL PROTEOSTASIS; COGNITIVE IMPAIRMENT;

D O I：

10.1016/j.mad.2021.111545

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Strategies to correct declining nicotinamide adenine dinucleotide (NAD+) levels in neurological disease and biological ageing are promising therapeutic candidates. These strategies include supplementing with NAD(+) precursors, small molecule activation of NAD+ biosynthetic enzymes, and treatment with small molecule inhibitors of NAD+ consuming enzymes such as CD38, SARM1 or members of the PARP family. While these strategies have shown efficacy in animal models of neurological disease, each of these has the mechanistic potential for adverse events that could preclude their preclinical use. Here, we discuss the implications of these strategies for treating neurological diseases, including potential off-target effects that may be unique to the brain.

引用

页数：13

共 176 条

[1] ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP(+) [J].

Aarhus, R ;

Graeff, RM ;

Dickey, DM ;

Walseth, TF ;

Lee, HC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (51) :30327-30333

[2] β-amyloid activates PARP causing astrocytic metabolic failure and neuronal death [J].

Abeti, Rosella ;

Abramov, Andrey Y. ;

Duchen, Michael R. .

BRAIN, 2011, 134 :1658-1672

[3] Perturbations of NAD+ salvage systems impact mitochondrial function and energy homeostasis in mouse myoblasts and intact skeletal muscle [J].

Agerholm, Marianne ;

Dall, Morten ;

Jensen, Benjamin A. H. ;

Prats, Clara ;

Madsen, Soren ;

Basse, Astrid L. ;

Graae, Anne-Sofie ;

Risis, Steve ;

Goldenbaum, Julie ;

Quistorff, Bjorn ;

Larsen, Steen ;

Vienberg, Sara G. ;

Treebak, Jonas T. .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2018, 314 (04) :E377-E395

[4] Regulation of intracellular levels of NAD: A novel role for CD38 [J].

Aksoy, Pinar ;

White, Thomas A. ;

Thompson, Michael ;

Chini, Eduardo N. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 345 (04) :1386-1392

[5] Mechanism of sirtuin inhibition by nicotinamide:: Altering the NAD+ cosubstrate specificity of a Sir2 enzyme [J].

Avalos, JL ;

Bever, KM ;

Wolberger, C .

MOLECULAR CELL, 2005, 17 (06) :855-868

[6] Identification of a new urate and high affinity nicotinate transporter, hOAT10 (SLC22A13) [J].

Bahn, Andrew ;

Hagos, Yohannes ;

Reuter, Stefan ;

Balen, Daniela ;

Brzica, Hrvoje ;

Krick, Wolfgang ;

Burckhardt, Birgitta C. ;

Sabolic, Ivan ;

Burckhardt, Gerhard .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (24) :16332-16341

[7] Neuroprotective efficacy of P7C3 compounds in primate hippocampus [J].

Bauman, Melissa D. ;

Schumann, Cynthia M. ;

Carlson, Erin L. ;

Taylor, Sandra L. ;

Vazquez-Rosa, Edwin ;

Cintron-Perez, Coral J. ;

Shin, Min-Kyoo ;

Williams, Noelle S. ;

Pieper, Andrew A. .

TRANSLATIONAL PSYCHIATRY, 2018, 8

[8] Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ (1-42)-induced rat model of Alzheimer's disease [J].

Bayrakdar, E. Turunc ;

Uyanikgil, Y. ;

Kanit, L. ;

Koylu, E. ;

Yalcin, A. .

FREE RADICAL RESEARCH, 2014, 48 (02) :146-158

[9] Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals QUANTITATIVE BASIS FOR Urh1 AND PURINE NUCLEOSIDE PHOSPHORYLASE FUNCTION IN NAD+ METABOLISM [J].

Belenky, Peter ;

Christensen, Kathryn C. ;

Gazzaniga, Francesca ;

Pletnev, Alexandre A. ;

Brenner, Charles .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (01) :158-164

[10] GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing [J].

Benyó, Z ;

Gille, A ;

Kero, J ;

Csiky, M ;

Suchánková, MC ;

Nüsing, RM ;

Moers, A ;

Pfeffer, K ;

Offermanns, S .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (12) :3634-3640

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