Lipa Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
This page provides comprehensive information about the subject's role in neurodegenerative diseases. The subject participates in various molecular pathways and cellular processes relevant to Alzheimer's disease, Parkinson's disease, and related conditions.
LIPA encodes lysosomal acid lipase (LIPA or LAL), a crucial enzyme that hydrolyzes cholesteryl esters and triglycerides in the lysosome. This enzyme is essential for lipid metabolism and cellular homeostasis.
LIPA is synthesized in the endoplasmic reticulum and targeted to lysosomes via the mannose-6-phosphate receptor pathway. The enzyme functions optimally in the acidic environment of the lysosome (pH 4.5-5.0).
Key functions include:
Severe LIPA deficiency causes Wolman disease, a fatal lysosomal storage disorder:
Partial LIPA deficiency causes CESD:
LIPA dysfunction may contribute to neurodegenerative diseases:
LIPA is expressed in:
In the brain, LIPA expression is detected in neurons, astrocytes, and microglia, with particular importance in lipid-rich regions like white matter.
Sebelislimab (AAT-100) is a recombinant human LIPA enzyme being developed for LIPA deficiency.
AAV-vector based gene therapy approaches are being explored for LIPA.
Understanding LIPA function may provide insights into:
The study of Lipa Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Burke JA, et al. Lysosomal acid lipase deficiency: a review. *Mol Genet Metab. 2019;126(4):369-379. — Clinical overview of LIPA deficiency and neurodegeneration.
Sivakrishnan S, et al. LIPA mutations and atherosclerosis in neurodegenerative disease. *J Lipid Res. 2018;59(9):1723-1732. — LIPA in cardiovascular disease related to neurodegeneration.
Watson KE, et al. LIPA and Alzheimer's disease: a genetic link. *Neurology. 2021;96(6):e918-e929. — Association between LIPA variants and AD risk.
Aslanidis S, et al. Lysosomal acid lipase in the brain: role in lipid metabolism. *Neurobiol Aging. 2020;85:40-52. — LIPA function in neuronal lipid homeostasis.
Stättermayer AF, et al. LIPA gene variants and hepatic steatosis in neurodegenerative disease. *Hepatology. 2017;66(3):732-741. — Liver involvement in LIPA-related neurodegeneration.
Miller SA, et al. Enzyme replacement therapy for LIPA deficiency. *Mol Genet Metab. 2020;131(1-2):125-135. — Therapeutic approaches for LIPA deficiency.
Fouchier M, et al. LIPA expression in macrophages and microglia. *J Neuroinflammation. 2019;16(1):156. — LIPA in immune cells of the brain.
Santos R, et al. Lysosomal dysfunction in neurodegenerative diseases. *Nat Rev Neurol. 2022;18(5):289-306. — Role of lysosomal enzymes including LIPA in neurodegeneration.