Abstract
Alzheimer’s disease (AD) and vascular dementia (VaD) are the two most common forms of dementia in older people. Although these two dementia types differ in their etiology, they share many pathophysiological and morphological features, including neuronal loss, which is associated with the microtubule (MT) destabilization. Stabilization of MTs is achieved in different ways: through interactions with MT binding proteins (MTBP) or by posttranslational modifications (PTMs) of tubulin. Polyglutamylation and tyrosination are two foremost PTMs that regulate the interaction between MTs and MTBPs, and play, therefore, a role in neurodegeneration. In this review, we summarize key information on tubulin PTMs in relation to AD and VaD and address the importance of studying further the tubulin code to reveal sites of potential intervention in development of novel and effective dementia therapy.
Highlights
Tubulin posttranslational modifications (PTMs) in Dementia Patientsvascular dementia (VaD) is the second most common form of dementia, accounting for ∼15% of all cases. In spite of the number of patients diagnosed and the annual costs for this syndrome being highly significant, VaD has not been as thoroughly studied as Alzheimer’s disease (AD) (Iadecola, 2013)
Reviewed by: Cathryn Louise Haigh, Rocky Mountain Laboratories (NIAID), United States Roland Brandt, University of Osnabrück, Germany
We summarize key information on tubulin posttranslational modifications (PTMs) in relation to Alzheimer’s disease (AD) and vascular dementia (VaD) and address the importance of studying further the tubulin code to reveal sites of potential intervention in development of novel and effective dementia therapy
Summary
VaD is the second most common form of dementia, accounting for ∼15% of all cases. In spite of the number of patients diagnosed and the annual costs for this syndrome being highly significant, VaD has not been as thoroughly studied as AD (Iadecola, 2013). VaD is considered a heterogeneous group of brain disorders since it can be caused by several cerebrovascular pathologies (Iadecola, 2013), such as atherosclerosis, small vessel disease or cerebral amyloid angiopathy (CAA), which is the accumulation of Aβ in vessel walls (Serrano-Pozo et al, 2011) These diseases, in turn, can lead to different cerebrovascular lesions, i.e., ischemic or hemorrhagic infarct, white matter lesions or hemorrhages (McAleese et al, 2016; Smith, 2017; Kalaria, 2018). AD and VaD differ in their etiology, they share risk factors, such as age, obesity, the apolipoprotein E4 allele (ApoE ε4 allele) and hypercholesterolemia (Akinyemi et al, 2013) They share similarities in their pathophysiology (Table 1; Kalaria and Ballard, 1999), i.e., a tendency of Aβ42 to be significantly higher in the temporal lobe (Lewis et al, 2006), or a neuronal cell volume loss (Gemmell et al, 2012). In isolated neuronal cultures, Aβ oligomers cause tau-dependent
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