The pathogenesis of, and pharmacological treatment for, Canavan disease

Huijun Wei; John R. Moffett; Man Amanat; Ali Fatemi; Takashi Tsukamoto; Aryan M. Namboodiri; Barbara S. Slusher

doi:10.1016/j.drudis.2022.05.019

The pathogenesis of, and pharmacological treatment for, Canavan disease

Huijun Wei
, John R. Moffett^*
, Man Amanat
, Ali Fatemi
, Takashi Tsukamoto
, Aryan M. Namboodiri
, Barbara S. Slusher

^*Corresponding author for this work

Anatomy, Physiology, and Genetics

Research output: Contribution to journal › Review article › peer-review

27 Scopus citations

Abstract

Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.

Original language	English
Pages (from-to)	2467-2483
Number of pages	17
Journal	Drug Discovery Today
Volume	27
Issue number	9
DOIs	https://doi.org/10.1016/j.drudis.2022.05.019
State	Published - Sep 2022

Keywords

Aspartate N-acetyltransferase (Asp-NAT)
Aspartoacylase (ASPA)
Canavan disease (CD)
N-acetylaspartate (NAA)
NaDC3

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10.1016/j.drudis.2022.05.019

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title = "The pathogenesis of, and pharmacological treatment for, Canavan disease",

abstract = "Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.",

keywords = "Aspartate N-acetyltransferase (Asp-NAT), Aspartoacylase (ASPA), Canavan disease (CD), N-acetylaspartate (NAA), NaDC3",

author = "Huijun Wei and Moffett, \{John R.\} and Man Amanat and Ali Fatemi and Takashi Tsukamoto and Namboodiri, \{Aryan M.\} and Slusher, \{Barbara S.\}",

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year = "2022",

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language = "English",

volume = "27",

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T1 - The pathogenesis of, and pharmacological treatment for, Canavan disease

AU - Wei, Huijun

AU - Moffett, John R.

AU - Amanat, Man

AU - Fatemi, Ali

AU - Tsukamoto, Takashi

AU - Namboodiri, Aryan M.

AU - Slusher, Barbara S.

PY - 2022/9

Y1 - 2022/9

N2 - Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.

AB - Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.

KW - Aspartate N-acetyltransferase (Asp-NAT)

KW - Aspartoacylase (ASPA)

KW - Canavan disease (CD)

KW - N-acetylaspartate (NAA)

KW - NaDC3

UR - https://www.scopus.com/pages/publications/85132436470

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DO - 10.1016/j.drudis.2022.05.019

M3 - Review article

C2 - 35636725

AN - SCOPUS:85132436470

SN - 1359-6446

VL - 27

SP - 2467

EP - 2483

JO - Drug Discovery Today

JF - Drug Discovery Today

IS - 9

ER -

The pathogenesis of, and pharmacological treatment for, Canavan disease

Abstract

Keywords

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