TABLE 1.

Long-chain acyl-coenzyme A synthetases (ACSLs) and nervous system diseases (NSDs).

	Genes*		Proteins*
Name	OMIM®	Location	Size (Amino acids)	Molecular mass (Da)	Function	Nervous system diseases associated with ACSLs
ACSL1	152,425	4q35.1	698	77,943	⊳ Catalyzes the conversion of long-chain FA to acyl-CoAs for both synthesis of cellular lipids ⊳ Preferred substrates: oleic acid and linoleic acid (Kanter et al., 2012)	◇ Glioma (Wang et al., 2018; Zhou et al., 2019; Xu et al., 2022) ◇ Amyotrophic lateral sclerosis (ALS) (Ben-Zaken et al., 2022)
ACSL3	602,371	2q36.1	720	80,420	⊳ Convert MUFAs (e.g.) into acyl-CoA that binds to membrane phospholipids ⊳ Preferred substrates: oleic acid, myristate, palmitate, arachidonate and eicosapentaenoate (Grevengoed et al., 2014)	◇ Glioma (Fujino et al., 1996, 1997; Van Horn et al., 2005; Qiu et al., 2020) ◇ Stroke (Li et al., 2022)
ACSL4	300,157	Xq23	711	79,188	⊳ Catalyzing PUFAs metabolism and shaping cellular lipid composition ⊳ Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified epoxyeicosatrienoic acids ⊳ Modulates prostaglandin E2 secretion. ⊳ Preferred substrates: arachidonate (Klett et al., 2017)	◆Central nervous system ◇ Glioma (Zhou et al., 2019; Cheng et al., 2020; Tan et al., 2020; Yee et al., 2020; Yi et al., 2020; Bao C. et al., 2021; Dattilo et al., 2021; Hacioglu and Kar, 2022; Kram et al., 2022; Miao et al., 2022) ◇ Cerebrovascular diseases: ischemic stroke (Gubern et al., 2013; Li et al., 2019; Chen J. et al., 2021; Cui et al., 2021; Guo H. et al., 2021; Li C. et al., 2021; Liao et al., 2021; Hu et al., 2022; Tuo et al., 2022), hemorrhage (Chen B. et al., 2021; Jin et al., 2021), subarachnoid hemorrhage (Qu et al., 2021; Huang et al., 2022; Yuan et al., 2022) ◇ Injury: traumatic brain injury (Kenny et al., 2019; Xiao et al., 2019; Bao Z. et al., 2021), spinal cord injury (Zhou et al., 2020; Pang et al., 2022) ◇ Intellectual disability: non-syndromic X-Linked intellectual developmental disorder (Meloni et al., 2009; Zhang et al., 2009; Liu et al., 2011, 2014; Huang et al., 2016; Chang et al., 2019; Jia et al., 2019), Alport syndrome with intellectual disability (Rodriguez et al., 2010; Smetana et al., 2021) ◇ Neurodegenerative diseases: Alzheimer’s disease (AD) (Rapoport, 2008; Thomas et al., 2017; Gao et al., 2021; Peng et al., 2021; Yan et al., 2022; Zhu et al., 2022), Parkinson’s disease (PD) (Li S. et al., 2021; Song et al., 2021) ◇ Cognitive dysfunction: diabetic cognitive impairment (An et al., 2022), postoperative cognitive dysfunction (POCD) (Cheng et al., 2021) ◇ Others: epilepsy (Kahn-Kirby et al., 2019; Mao et al., 2019; Shao et al., 2020, 2022; Yang et al., 2020; Chen et al., 2022), ALS (Moujalled et al., 2021; Zilka et al., 2021; Wang T. et al., 2022), cerebral malaria (Liang et al., 2022), bipolar disorder (BD) (Modi et al., 2014, 2017), sepsis-associated encephalopathy (SAE) (Wang J. et al., 2022)	◆Peripheral nervous system ◇ Neuropathic pain (NP) induced by peripheral nerve injury <ref> (Zhang X. et al., 2022; Guo Y. et al., 2021; Wang et al., 2021)
ACSL5	605,677	10q25.2	683	75,991	⊳ Activates FA from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage ⊳ Preferred substrates: palmitate, palmitoleate, oleate, linoleate (Klett et al., 2017)	◇ Glioma (Yamashita et al., 2000; Mashima et al., 2009a,b) ◇ ALS (Iacoangeli et al., 2020; Nakamura et al., 2020; Saez-Atienzar et al., 2021)
ACSL6	604,443	5q31	697	77,752	◇ FA metabolism in brain ◇ Preferred substrates: It has equal preference for saturated and PUFAs with a backbone of C16–C20 (Lopes-Marques et al., 2013)	◇ AD (Pontifex et al., 2021) ◇ Schizophrenia (Chen et al., 2006, 2011; Chowdari et al., 2007)

ACSL, long-chain acyl-coenzyme A synthetase; FA, fatty acids; MUFAs, monounsaturated fatty acids; PUFAs, polyunsaturated fatty acids; OMIM, Online Mendelian Inheritance in Man. *Data from GeneCards (http://www.genecards.org/) and OMIM (https://omim.org/about).