The Role of Cysteine Protease in Alzheimer Disease

Hasanbašić, Samra; Jahić, Alma; Karahmet, Enver; Sejranić, Asja; Prnjavorac, Besim

doi:10.5455/msm.2016.28.235-238

Cited by 27 publications

(20 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have established that CATB is induced in the mouse model of AD expressing human mutant APP variant and plays a crucial role in amyloidogenesis observed in these animals [20,65]. When CATB in the brain of AD mice was depleted genetically or inhibited pharmacologically by administration of cysteine protease inhibitor E64d, the amyloid deposition and cognitive decline were delayed, suggesting that the enzyme may become a potential drug target for AD [34,36,43,[66][67][68].…”

Section: Discussionmentioning

confidence: 99%

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Viana

Gonzalez

Alvarez

et al. 2020

IJMS

View full text Add to dashboard Cite

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of α-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of β-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Viana

Gonzalez

Alvarez

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Cysteine plays a vital role in the synthesis of essential fatty acids, and therefore, it is important for cell membrane and nerve myelin sheaths especially on axon endings (Sameem et al., 2019). Through shielding axons from oxidative stress, cysteine can prevent major neurodegenerative disorders such as Parkinson's or Alzheimer's and underlying stress (Hasanbasic, Jahic, Karahmet, Sejranic, & Prnjavorac, 2016). Moreover, dietary L‐cysteine supplementation can improve the lipid metabolism (Yin et al., 2016).…”

Section: Role Of Cysteine In the Bodymentioning

confidence: 99%

Cysteine and homocysteine as biomarker of various diseases

Rehman

Shabbir

Inam‐Ur‐Raheem

et al. 2020

Food Science & Nutrition

166

View full text Add to dashboard Cite

Cysteine and homocysteine (Hcy), both sulfur‐containing amino acids (AAs), produced from methionine another sulfur‐containing amino acid, which is converted to Hcy and further converted to cysteine. This article aims to highlight the link between cysteine and Hcy, and their mechanisms, important functions, play in the body and their role as a biomarker for various types of diseases. So that using cysteine and Hcy as a biomarker, we can prevent and diagnose many diseases. This review concluded that hyperhomocysteinemia (elevated levels of homocysteine) is considered as toxic for cells and is associated with different health problems. Hyperhomocysteinemia and low levels of cysteine associated with various diseases like cardiovascular diseases (CVD), ischemic stroke, neurological disorders, diabetes, cancer like lung and colorectal cancer, renal dysfunction‐linked conditions, and vitiligo.

show abstract

“…Neuronal survival, by protecting against apoptosis, hypoxic stress, and nitric oxide toxicity, is also influenced by insulin signaling [26]. Accelerated apoptosis is one of the most important factors for AD development [27] Structural brain changes including whole-brain [28] and medial temporal atrophy [29] are linked to dysfunctional insulin signaling. AD and type 2 diabetes mellitus are two of the most common diseases in elder population.…”

Section: Influence Of Insulin To Microenviromental Changes In Brain Imentioning

confidence: 99%

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Karahmet¹,

Prnjavorac²,

Sejranić³

et al. 2018

J Alzheimers Dis Parkinsonism

Self Cite

View full text Add to dashboard Cite

IntroductionAlzheimer's disease characterized clinically by a progressive and gradual decline in cognitive function and neuropathologically, by the presence of neuronal threats, specific neuron loss, synapse loss and disturbance of cholinergic synapses. Most people with Alzheimer's have the late-onset form of the disease, in which the symptoms become apparent in their mid-60s. Genetic Basis of Metabolic Changes in Alzheimer's DiseasesThe apolipoprotein E (APOE) gene is involved in late-onset Alzheimer's. This gene has several forms. One of them, APOE ε4, increases a person's risk of developing AD and is associated with an earlier age onset. Around 0.1% of the cases are familial forms of autosomal dominant inheritance, which has an onset before age 65 [1]. This form of the disease is known as onset familial Alzheimer's disease. Most of the autosomal dominant familial AD can be attributed to mutations in one of three genes: those encoding amyloid precursor protein (APP) and presenilins1 and 2 [2]. Most of the mutations in the APP and presenilin genes increase the production of a small protein called Aβ42, which is the main component of senile plaques [3]. Some of the mutations merely alter the ratio between Aβ42 and the other major forms particularly Aβ40 without increasing Aβ42 levels [4,5]. The major hallmarks of AD pathology are masses of the extracellular β-amyloid peptide (Aβ) and neurofibrillary tangles of the microtubule binding protein tau [6,7]. Aβ has crucial importance in the relation of AD as well as the crucial role of its pathogenesis. The neurotoxic potential of the Aβ peptide results from its biochemical properties, favoring aggregation into insoluble oligomers and protofibrils [7]. Etiological treatment of AD is AbstractAlzheimer disease (AD) is common worldwide and almost every case has comorbidities. One of the most common comorbidities of AD is Diabetes mellitus (DM), with or without metabolic syndrome. Both diseases effect nerve tissue and successful treatment would improve the status of the patient. In patients with Alzheimer disease treatment of DM, the treatment could be harmful to the AD, because of that high insulin intake. This may lead to progression of AD. Insulin is considered the best treatment for DM, but insulin therapy could increase comorbidity with AD. No specific therapy for AD is known up to date, so because of that DM is one of the most important risk for AD, concomitant therapy for DM should be planned very carefully. All options of DM therapy should be considered, and different mechanisms of anti-diabetic drugs are preferable. Treatment of AD is more complex metabolic syndrome is present. Any inflammation causes local tissue damage, including brain tissue during AD. Release of interleukins, primarily TNF-α, IL-6, IL-1β in the presence of adipokine leptin, maintains chronic inflammatory status in local brain tissue. Thus, low doses of immunosuppressant therapy should be considered for treatment of AD in future. To delay apoptosis of nerve tissue cells, brain and nerve tissue...

show abstract

The Role of Cysteine Protease in Alzheimer Disease

Cited by 27 publications

References 42 publications

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Cysteine and homocysteine as biomarker of various diseases

Does the Choice of Treatment of Diabetes Mellitus Change Natural Course of Alzheimer Disease?

Contact Info

Product

Resources

About