Defects in the autophagy-lysosomal degradation pathway contribute to neurodegenerative diseases. Cathepsins B (CtsB) and L (CtsL) are major lysosomal cysteine proteases. Mice deficient in both CtsB and CtsL exhibit abnormalities not only in neural tissue but in other organs, such as heart and liver, with most dying at approximately 16 days of age. To investigate the roles of CtsB and CtsL in the nervous system, nervous system–specific CTSB and CTSL double-knockout mice (CtsB/L-NES) were gener...

Drug resistance is a major challenge in cancer therapy, and the expression of efflux pumps such as P-glycoprotein (P-gp, ABCB1) often correlates with poor prognosis in various tumors, including glioblastoma (GB). Considering that different roles for these proteins have been established in the biology of various tumors, this study aimed to investigate the functions of P-gp in GB-derived cells by evaluating its survival, migratory, and apoptosis-regulating capabilities, as well as its potential...

The role that neurotrophins, such as nerve growth factor, play in the pathogenesis of neurodegenerative diseases has long been appreciated. However, the neuregulin (NRG) family of growth factors and/or their v-erb-B2 avian erythroblastic leukemia viral oncogene homolog (ERBB) receptors have also been implicated in the pathogenesis of conditions, such as Alzheimer disease (AD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). In this review, we consider i) the...

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the virus's impact on the central nervous system and its potential to exacerbate neurodegenerative diseases, like Alzheimer disease (AD). Emerging evidence suggests that SARS-CoV-2 infection contributes to chronic neuroinflammation, a key driver in the etiopathogenesis of AD. Shared mechanisms, including blood-brain barrier (BBB) dysfunction, systemic infla...

Alzheimer disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority. In parallel with the number of patients with AD, the number of cancer survivors is estimated to increase significantly, and up to 80% of cancer patients treated with chemotherapy will develop cognitive defi...

Alzheimer’s disease (AD) is a chronic multifactorial neurodegenerative disease affecting a large proportion of the elderly population with detrimental psychological and socioeconomic impacts. This review starts with a brief overview of the molecular aspects of AD. It aims to provide recent updates on several potential protein targets studied as valid therapeutic approaches such as Bassoon protein, triggering receptor expressed on myeloid cells 2 (TREM2), phosphorylated tau (chimeric molecules...

Exposure to repeated head impacts (RHI), such as those experienced in contact sports or military service, can lead to the development of chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. CTE cannot be diagnosed during life, only by post-mortem neuropathological exam. The pathognomonic lesion of CTE consists of a perivascular accumulation of hyperphosphorylated tau (p-tau) as neurofibrillary tangles and dotlike neurites, preferentially at the depths of cortical sulci. The ...

Computational neurodegenerative neuropathology represents a transformative approach in the analysis and understanding of neurodegenerative diseases through utilization of whole slide images (WSIs) and advanced machine learning/artificial intelligence (ML/AI) techniques. This review explores the emerging field of computational neurodegenerative neuropathology, emphasizing its potential to enhance neuropathologic assessment, diagnosis, and research. Recent advancements in ML/AI technologies hav...

Cognitive impairment due to vascular pathology was recognized by Otto Binswanger in 1894, before Alois Alzheimer presented his findings in 1907. Vascular causes of cognitive impairment are likely due to a range of pathologies that are still, a hundred years later, unknown. Recent epidemiological evidence from post-mortem human brains report cases may be afflicted by Alzheimer’s disease, vascular disease or both. Although it is well-known that hypertension and diabetes affect vasculature throu...

Neurodegenerative diseases, including Alzheimer disease, frontotemporal dementia, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis, are often casually linked to protein aggregation and inclusion. As the origins of those proteinopathies have been biochemically traced and genetically mapped, genetically engineered animal models carrying the specific mutations or variants are widely used for investigating the etiology of these diseases, as well as for testing potential th...