Table 1 Diseases related with lysosomal dysfunction

Atherosclerosis

Lysosomal acid lipase deficient

Substantial decrease in lysosomal acid lipase activity leads to premature atherosclerosis in human

[57]

OxLDL or cholesterol crystal accumulation

OxLDL or cholesterol crystal causes lysosomal membrane permeability, autophagy deficient, mitochondrial dysfunction, inflammasome activation, and apoptosis

[54, 58, 61,62,63]

Neurodegeneration diseases

Alzheimer's disease

Presenilin 1 mutation

Defective Presenilin 1-dependent lysosomal acidification is one of the main causes of early-onset familial AD

[93,94,95, 340, 341]

Becn1 ablation

Heterozygous deletion of beclin 1 (Becn1) results in autophagy disruption, Aβ deposition, and neurodegeneration

[97]

Cathepsin D mutation

The T-allele of cathepsin D rs17571 increases risk of AD

[92]

Cathepsin B ablation

Ablation of cathepsin B increases the abundance of Aβ42 and potentiates plaque deposition

[91]

Parkinson’s disease

Snca mutation

A53T point mutation in the Snca gene causes familial PD

[107, 108]

Atp13a2 ablation

Atp13a2 depletion leads to lysosomal membrane instability, impaired acidification, blocked clearance of autophagosomes, α-syn accumulation, and cell death

[109, 110]

Gba1 mutation

Mutations in the Gba1 gene are important risk factors for PD

[113]

Huntington disease

Htt mutation

Mutated HTT protein has abnormally long polyglutamine (polyQ) repeats near the N-terminus, which promotes formation of toxic oligomers and neuronal inclusion bodies

[119, 120]

Wdfy3 ablation

Depletion of Wdfy3 accelerates the accumulation of polyQ aggregates

[127]

Sqstm1 knockdown

Sqstm1 knockdown increases mHTT-induced cell death

[128]

Pancreatitis

Impaired autophagy flux

Increased autophagosome formation and decreased autophagosome clearance are observed

[140, 342]

Imbalanced cathepsin B and cathepsin L

Imbalance between cathepsin B and cathepain L contributes to accumulation of activated intracellular trypsin

[140]

Autoimmune disorders

Systemic lupus erythematosus

Enhanced autophagy in T cells

Enhanced autophagy causes imbalanced T cell subsets

[146,147,148]

Defect LC3-associated phagocytosis

Defect LC3-associated phagocytosis leads to blunted clearance of dying cells and elevated inflammation

[149]

Defect lysosomal acidification

Macrophages in lupus shows elevated lysosomal pH

[343]

Crohn’s disease

Defect autophagy

Human or mice deficient in ATG16L1 are more susceptible to Crohn’s disease

[150, 151]

Defect lysosomal acidification

Elevated luminal pH links lysosomal dysfunction with Crohn’s disease risk

[344]

Rheumatoid arthritis

Impaired autophagy

Reduced autophagy links altered metabolism and T cell exhaustion

[152]

Multiple sclerosis

Enhanced autophagy

Enhanced ATG5 expression in T cells is correlated with more sever disability

[153]

Lysosomal storage disorder

Niemann-Pick type C (NPC) disease

Npc1 or Npc2 mutation

Defective NPC1 or NPC2 causes lysosomal accumulation of cholesterol and glycosphingolipids leading to hepatic, pulmonary, and neuropsychiatric disorder

[345]

Fabry disease

Galactosidase α mutation

Galactosidase α mutation causes globotriaosylceramide accumulation in lysosomes leading to vascular diseases

[346]

Tay-Sachs disease

β-hexosaminidase α mutation

Deficient β-hexosaminidase α causes GM2 ganglioside accumulation in lysosomes of nerve cells leading to neuro disorder

[347]

Mucopolysaccharidoses diseases

Mutation in mucopolysaccharide catabolic enzymes

Lysosomal accumulation of mucopolysaccharides leads to disorders in bone, cartilage, connective tissues, and nervous

[348]

Pompe disease

α glucosidase mutation

Mutated α glucosidase causes glycogen accumulation in lysosomes leading to cardiac and respiratory failure

[349]

Gaucher disease

glucosylceramidase β mutation

Glucosylceramide accumulates in macrophage lysosomes leading to disorder in visceral organs and nervous system

[162]